Plasma membranes are subject to continuous deformations. Strikingly, some of these transient membrane undulations yield membrane‐associated signaling hubs that differ in composition and function, depending on membrane geometry and the availability of co‐factors. Here, recent advancements on this ubiquitous type of receptor‐independent signaling are reviewed, with a special focus on emerging concepts and technical challenges associated with studying these elusive signaling sites.

Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by (...) different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. (shrink)

The cellular capacity to internalise objects, involving attachment, engulfment and uptake, exists in virtually all organisms. Many uptake reactions are associated with cell signalling. However, the mechanical forces that form endocytotic vesicles are not known. We propose a ‘leverage‐mediated’ uptake mechanism involving lateral cross‐linking processes on the cell surface that can generate the configurational energy to create an inverse curvature of the membrane. BioEssays 26:1344–1350, 2004. © 2004 Wiley Periodicals, Inc.

Lipid droplets (LDs) are ubiquitous, neutral lipid storage organelles that act as hubs of metabolic processes. LDs are structurally unique with a hydrophobic core that mainly consists of neutral lipids, sterol esters, and triglycerides, enclosed within a phospholipid monolayer. Nascent LD formation begins with the accumulation of neutral lipids in the endoplasmic reticulum (ER) bilayer. The ER membrane proteins such as seipin, LDAF1, FIT, and MCTPs are reported to play an important role in the formation of nascent LDs. As (...) the LDs grow, they unmix from the highly charged ER membrane to form mature LDs. LD biogenesis is an exciting, emerging research area, and herein, we discuss the recent progress in our understanding of the formation of eukaryotic nascent LDs. We focus on the role of ER membrane shaping proteins such as reticulons and reticulon‐like proteins, membrane lipids, and cytoskeleton proteins such as septin in the formation of nascent LDs. (shrink)

Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane‐associated state, only RalA can be extracted from the membrane by CaM and this non‐canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would (...) lead to CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy. (shrink)

It is common to say that the origin of the membrane potential is attributed to transmembrane ion transport, but it is theoretically possible to explain its generation by the mechanism of ion adsorption. It has been previously suggested that the ion adsorption mechanism even leads to potential formulae identical to the famous Nernst equation or the Goldman-Hodgkin-Katz equation. Our further analysis, presented in this paper, indicates that the potential formula based on the ion adsorption mechanism leads to an equation (...) that is a function of the surface charge density of the material and the surface potential of the material. Furthermore, we have confirmed that the equation holds in all the different experimental systems that we have studied. This equation appears to be a key equation that governs the characteristics of the membrane potential in all systems. (shrink)

One persistent puzzle in the life sciences is the asymmetric lipid composition of the cellular plasma membrane: while the exoplasmic leaflet is enriched in lipids carrying predominantly saturated fatty acids, the cytoplasmic leaflet hosts preferentially lipids with (poly‐)unsaturated fatty acids. Given the high energy requirements necessary for cells to maintain this asymmetry, the question naturally arises regarding its inherent benefits. In this paper, we propose asymmetry to represent a potential solution for harmonizing two conflicting requirements for the plasma (...) class='Hi'>membrane: first, the need to build a barrier for the uncontrolled influx or efflux of substances; and second, the need to form a fluid and dynamic two‐dimensional substrate for signaling processes. We hence view here the plasma membrane as a composite material, where the exoplasmic leaflet is mainly responsible for the functional integrity of the barrier and the cytoplasmic leaflet for fluidity. We reinforce the validity of the proposed mechanism by presenting quantitative data from the literature, along with multiple examples that bolster our model. (shrink)

Wesley C. Salmon (1977) has written a characteristically elegant and ingenious paper 'The Curvature of Physical Space'. He argues in it that the curvature of a space cannot be intrinsic to it. Salmon relates his view that space is affinely amorphous to Grunbaum's view (Grunbaum 1973, esp. Ch. 16 & 22) that it is metrically amorphous and acknowledges parallels between the arguments which have been offered for each opinion. I wish to dispute these conclusions on philosophical grounds quite as much (...) as on geometrical ones. Although I concentrate most on arguing for a well defined, intrinsic affinity for physical space the arguments extend easily to support a well defined, intrinsic metric. (shrink)

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...) maintenance of ERGIC membranes are poorly defined. However, recent evidence suggests an important role for Trk‐fused gene (TFG) in regulating the integrity of the ER/ERGIC interface. Moreover, in the absence of cytoskeletal elements to scaffold tracks on which COPII carriers might move, TFG appears to promote anterograde cargo transport by locally tethering COPII carriers adjacent to ERGIC membranes. This action, regulated in part by the intrinsically disordered domain of TFG, provides sufficient time for COPII coat disassembly prior to heterotypic membrane fusion and cargo delivery to the ERGIC. -/- . (shrink)

Extracorporeal membrane oxygenation (ECMO) is a form of life support for cardiac and/or pulmonary failure with unique ethical challenges compared to other forms of life support. Ethical challenges with ECMO exist when conventional standards of care apply, and are exacerbated during periods of absolute ECMO scarcity when “crisis standards of care” are instituted. When conventional standards of care apply, we propose that it is ethically permissible to withhold placing patients on ECMO for reasons of technical futility or when patients (...) have terminal, short-term prognoses that are untreatable by ECMO. Under crisis standards of care, it is ethically permissible to broaden exclusionary criteria to also withhold ECMO from patients who have a low likelihood of recovery, to maximize the overall number of lives saved. Unilateral withdrawal of ECMO against a patient’s preferences is unethical under conventional standards of care, but is ethical under crisis standards of care to increase access to ECMO to others in society. ECMO should only be rationed when true scarcity exists, and allocation protocols should be transparent to the public. When rationing must occur under crisis standards of care, it is imperative that oversight bodies assess for inequities in the allocation of ECMO and make frequent changes to improve any inequities. (shrink)

The internationally renowned physicist Harald Fritzsch deftly explains the meaning and far-flung implications of the general theory of relativity and other mysteries of modern physics by presenting an imaginary conversation among Newton, Einstein, and a fictitious contemporary particle physicist named Adrian Haller--the same device Fritzsch employed to great acclaim in his earlier book An Equation That Changed the World, which focused on the special theory of relativity. Einstein's theory of gravitation, his general theory of relativity, touches on basic questions of (...) our existence. Matter, according to Einstein, has no existence independent of space and time. It is even capable of bending the structure of space and changing the course of time--it introduces a "curvature." Gravity emerges not as an actual physical force but as a consequence of space-time geometry. Even the apple that drops from the tree follows the curvature of time and space. In this entertaining and involving account of relativity, Newton serves as the skeptic and asks the questions a modern reader might ask. Einstein himself does the explaining, while Haller explains the new developments that have occurred since the general theory was proposed. The result is an intellectual roller-coaster ride in which concepts that have entered the vernacular become clear for the first time: the Big Bang, "black holes," elementary particles, and much more. (shrink)

Integral membrane proteins are found in all cellular membranes and fulfil many of the functions that are central to life. A critical step in the biosynthesis of membrane proteins is their insertion into the lipid bilayer. The mechanisms of membrane protein insertion and folding are becoming increasingly better understood, and efficient methods for the ab initio prediction of three‐dimensional protein structure from the primary amino acid sequence may be within reach. Already, the basic tools needed for engineering (...) and de novo design of integral membrane proteins seem to be at hand. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor (...) of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

The renormalization group is used to analyze the behavior of certain gravitationally significant renormalized coupling constants under a scaling of the spacetime curvature. After discussing a simple example, the results are summarized for a class of grand unified theories.

Microfilament interactions with the plasma membranes of animal cells appear to vary with cell type and localization. In the erythrocyte, actin oligomers are associated with the membrane via spectrin and ankyrin. The ends of stress fibers in cultured cells, such as fibroblasts, are attached to the plasma membrane at focal adhesion sites and may involve the protein vinculin as a linking protein. In intestinal brush border microvilli a 110,000 dalton protein links the microfilament bundles to sites on the (...) microvillus. A transmembrane complex containing actin stably associated with a cell surface glycoprotein can be isolated from ascites tumor cell microvilli and can be obtained still associated with microfilaments by gentle extraction and gradient centrifugation of the microvilli. These varied interaction mechanisms are believed to be needed to satisfy the different structural and dynamic requirements of the particular systems. (shrink)

The human immune system can directly lyse invading micro‐organisms and aberrant host cells by generating pores in the cell envelope, called membrane attack complexes (MACs). Recent studies using single‐particle cryoelectron microscopy have revealed that the MAC is an asymmetric, flexible pore and have provided a structural basis on how the MAC ruptures single lipid membranes. Despite these insights, it remains unclear how the MAC ruptures the composite cell envelope of Gram‐negative bacteria. Recent functional studies on Gram‐negative bacteria elucidate that (...) local assembly of MAC pores by surface‐bound C5 convertase enzymes is essential to stably insert these pores into the bacterial outer membrane (OM). These convertase‐generated MAC pores can subsequently efficiently damage the bacterial inner membrane (IM), which is essential for bacterial killing. This review summarizes these recent insights of MAC assembly and discusses how MAC pores kill Gram‐negative bacteria. Furthermore, this review elaborates on how MAC‐dependent OM damage could lead to IM destabilization, which is currently not well understood. A better understanding on how MAC pores kill bacteria could facilitate the future development of novel strategies to treat infections with Gram‐negative bacteria. (shrink)

The biological membranes of eukaryotic cells harbor sensitive surveillance systems to establish, sense, and maintain characteristic physicochemical properties that ultimately define organelle identity. They are fundamentally important for membrane homeostasis and play active roles in cellular signaling, protein sorting, and the formation of vesicular carriers. Here, we compare the molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of fatty acid desaturation and the response to unfolded proteins and lipid bilayer stress in order to identify their (...) commonalities and specializations. We will speculate on the cellular significance of membrane property sensors in other organelles and discuss their putative mechanisms. Based on these findings, we propose membrane property sensors as an emerging class of proteins with wide implications for organelle communication and function. (shrink)

The Bianchi Identities relating asymmetric curvature to torsion are obtained as a new set of equations governing second-order curvature tensors. The usual contribution of symmetric curvature to the gravitational field is found to be a subset of these identities though with an added contribution due to torsion gradients. The antisymmetric curvature two-tensor is shown to be related to the divergence of the torsion. Using a model of particle-antiparticle pair production, identification of certain torsion components with electroweak fields is proposed. These (...) components obey equations, similar to Maxwell's, that are subsets of these linear Bianchi identities. These results are shown to be consistent with gauge and other previous analyses. (shrink)

Two kinds of membrane contacts in the vertebrate lens are described. Fiber gap junctions are domains where small molecules can pass between lens cells. Membrane structures of ball‐and‐socket type interlock adjacent lens fibers and thus contribute to the structural integrity of the lens. Both of these membrane contacts appear crucial for the maintenance of lens transparency.

In this article, it is hypothesized that a fundamental chemical reactivity exists between some non‐lipid constituents of cellular membranes and ester‐based lipids, the significance of which is not generally recognized. Many peptides and smaller organic molecules have now been shown to undergo lipidation reactions in model membranes in circumstances where direct reaction with the lipid is the only viable route for acyl transfer. Crucially, drugs like propranolol are lipidated in vivo with product profiles that are comparable to those produced in (...) vitro. Some compounds have also been found to promote lipid hydrolysis. Drugs with high lytic activity in vivo tend to have higher toxicity in vitro. Deacylases and lipases are proposed as key enzymes that protect cells against the effects of intrinsic lipidation. The toxic effects of intrinsic lipidation are hypothesized to include a route by which nucleation can occur during the formation of amyloid fibrils. (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation (...) and dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

The synthesis of biological membranes requires the insertion of proteins into a lipid bilayer. The rough endoplasmic reticulum of eukaryotic cells is a principal site of membrane biogenesis. The insertion of proteins into the membrane of the endoplasmic reticulum is mediated by a resident proteinaceous machinery. Over the last five years several different experimental approaches have provided information about the components of the machinery and how it may function.

Since the early nineteenth century a membrane or wall has been central to the cell’s identity as the elementary unit of life. Yet the literally and metaphorically marginal status of the cell membrane made it the site of clashes over the definition of life and the proper way to study it. In this article I show how the modern cell membrane was conceived of by analogy to the first “artificial cell,” invented in 1864 by the chemist Moritz (...) Traube (1826–1894), and reimagined by the plant physiologist Wilhelm Pfeffer (1845–1920) as a precision osmometer. Pfeffer’s artificial cell osmometer became the conceptual and empirical basis for the law of dilute solutions in physical chemistry, but his use of an artificial analogue to theorize the existence of the plasma membrane as distinct from the cell wall prompted debate over whether biology ought to be more closely unified with the physical sciences, or whether it must remain independent as the science of life. By examining how the histories of plant physiology and physical chemistry intertwined through the artificial cell, I argue that modern biology relocated vitality from protoplasmic living matter to nonliving chemical substances—or, in broader cultural terms, that the disenchantment of life was accompanied by the (re)enchantment of ordinary matter. (shrink)

It has long been known that the red blood cell contains a membrane skeleton that stabilizes the plasma membrane, determines its shape, and regulates the lateral distribution of the membrane glyco‐proteins to which it is attached. The way in which these functions are regulated in other cells has not been understood. It has now been shown that platelets also contain a membrane skeleton. In contrast to the membrane skeleton of the red blood cell, the platelet (...) membrane skeleton has actin‐binding protein, not spectrin, as a major component. The platelet membrane skeleton regulates the same cellular functions as the red blood cell membrane skeleton. Other cells may contain a membrane skeleton that is critical to their viability and normal functioning. (shrink)

This paper considers two among the several points of intersection in the work of Roberto Esposito and Jacques Derrida. First, and most obviously: in the context of conceptualizing community, and more broadly, Esposito and Derrida have elaborated concepts of immunity and auto-immunity to refer to auto-destructive modes of defense which profoundly threaten what – seemingly – ought to have been safeguarded through their mechanism. The second point of proximity is the use both make of figures of maternity and birth in (...) these conceptualizations. This comparison not only illuminates the differing philosophical commitments of Derrida and Esposito but also offers a means of challenging the fate of sexual difference in the work of Esposito. (shrink)

The liver was used widely in early studies of polarised transport but has been largely overlooked in recent years, mostly because of the development of epithelial cell lines which provide more tractable experimental systems. The majority of membrane proteins and lipids reach the hepatocyte apical membrane by transcytosis and it remains unclear whether there is a direct route for apical targeting, although the pathways present have yet to be fully characterised. The recent development of systems that allow hepatocyte (...) transport processes to be studied in culture and the observation that transcytosis can be significantly stimulated under physiological conditions suggest that hepatocytes have a role to play in future studies of polarised transport. This review discusses the known features of polarised membrane traffic in hepatocytes and contrasts them with the characteristics of vesicular transport in other epithelial cell types. (shrink)

This paper presents a philosophical analysis of the structure of black holes, focusing on the event horizon and its fundamental status. While black holes have been at the centre of countless paradoxes arising from the attempt to merge quantum mechanics and general relativity, recent experimental discoveries have emphasised their importance as objects for the development of Quantum Gravity. In particular, the statistical mechanical underpinning of black hole thermodynamics has been a central research topic. The Quantum Membrane Paradigm, proposed by (...) Wallace (Stud Hist Philos Sci Part B 66:103-117, 2019), posits a real membrane made of black hole microstates at the black hole horizon to provide a statistical mechanical understanding of black hole thermodynamics from an exterior observer’s point of view. However, we argue that the Quantum Membrane Paradigm is limited to low-energy Quantum Gravity and needs to be modified to avoid reference to geometric notions, such as the event horizon, which presumably do not make sense in the non-spatiotemporal context of full Quantum Gravity. Our proposal relies on the central dogma of black hole physics. It considers recent developments, such as replica wormholes and entanglement wedge reconstruction, to provide a new framework for understanding the nature of black hole horizons in full Quantum Gravity. (shrink)

In the context of 1960s research on biological membranes, scientists stumbled upon a curiously coloured material substance, which became called the “purple membrane.” Interactions with the material as well as chemical analyses led to the conclusion that the microbial membrane contained a photoactive molecule similar to rhodopsin, the light receptor of animals’ retinae. Until 1975, the find led to the formation of novel objects in science, and subsequently to the development of a field in the molecular life sciences (...) that comprised biophysics, bioenergetics as well as membrane and structural biology. Furthermore, the purple membrane and bacteriorhodopsin, as the photoactive membrane transport protein was baptized, inspired attempts at hybrid bio-optical engineering throughout the 1980s. A central motif of the research field was the identification of a functional biological structure, such as a membrane, with a reactive material substance that could be easily prepared and manipulated. Building on this premise, early purple membrane research will be taken as a case in point to understand the appearance and transformation of objects in science through work with material substances. Here, the role played by a perceptible material and its spontaneous change of colour, or reactivity, casts a different light on objects and experimental practices in the late twentieth century molecular life sciences. With respect to the impact of chemical working and thinking, the purple membrane and rhodopsins represent an influential domain straddling the life and chemical sciences as well as bio- and material technologies, which has received only little historical and philosophical attention. Re-drawing the boundary between the living and the non-enlivened, these researches explain and model organismic activity through the reactivity of macromolecular structures, and thus palpable material substances. (shrink)

Undoubtedly the Penrose-Hameroff Orch OR model may be considered as a good theory for describing information processing mechanisms and holistic phenomena in the human brain, but it doesn’t give us satisfactory explanation of human perception. In this work a new approach explaining our perception is introduced, which is in good agreement with Orch OR model and other mainstream science theories such as string theory, loop quantum gravity and holographic principle. It is shown that human perception cannot be explained in the (...) terms of elementary particles and we should introduce new indivisible holistic objects with geometry based on smooth infinitesimal analysis - elastic membranes. The example of such a membrane is our Universe which is an indivisible whole. It is shown that our perception may be considered as the result of elastic oscillations of two dimensional (2D) elastic membranes with closed topology embedded in our bodies. Only one elastic membrane responsible for its perceptions will correspond to the selected organism, but there may be other membranes, even at the cell level. In other words, reality may be considered as the process of time evolution of holistic energetically very weak macro objects - elastic membranes with the geometry based on smooth infinitesimal analysis. An embedded membrane in this multidimensional world will look different for the external and internal observers: from the outside it will look like a material object with smooth infinitesimal geometry, while from the inside our Universe-like space-time fabric. When interacting with elementary particles and other membranes, a membrane will transform their energy into its elastic energy (a new form of energy) - the energy of stretching of the infinitesimal segments. The theory postulates that these elastic deformations will not be observable from the point of view of the internal observer. Heisenberg’s uncertainty principle will work in this physics only from the point of view of the internal observer. For the external observer each embedded elastic membrane may be stretched and even a very small region will become observable. For example, living organisms play the role of internal observers of the Universe, and at the same time they serve as external observers for 2D membranes embedded into our Universe. We can observe our 2D self-membranes through our perceptions, which are encoded in elastic oscillations of the elastic membrane. According to the theory, elastic membranes occupy energetically favorable positions around microtubules involved into Orch OR. The theory not only gives us a really multidimensional holistic picture of reality, but it also provides us with a new method for understanding such phenomena as perception, self-awareness and will. (shrink)

Nous sommes à l'âge de la membrane, telle est une des thèses politiques que défend et explicite ce livre, ce concept se réclamant à la fois du biopouvoir de Foucault et des analyses de la membrane qui caractérise le vivant selon Simondon. Cette membrane est entrée, après la Seconde Guerre mondiale, dans une nouvelle époque, celle du " vivantisme " (où toutes les formes de vie se valent), du néolibéralisme et des réseaux financiers. Est-ce à dire que (...) toute politique n'est plus que branchée sur la membrane, productrice de celle-ci ou résistance à ses déchirements? Mais ce serait oublier que la politique dépend de gestes, autre thèse de ce livre. Même la membrane a son geste. L'auteur définit l'émancipation par l'effectuation de véritables enchaînements de gestes en résonance avec d'autres (champ, chair, espace gestuel). Or, puisque la membrane n'est pas émancipatrice, tout geste-événement ouvrant un champ est un trou dans la membrane. I l n'est donc pas question de résister mais de trouer la membrane. (shrink)

Extracellular ATP released from necrotic cells in inflamed tissues activates the P2X7 receptor, stimulates the exposure of phosphatidylserine, and causes cell lysis. Recent findings indicated that XK, a paralogue of XKR8 lipid scramblase, forms a complex with VPS13A at the plasma membrane of T cells. Upon engagement by ATP, an unidentified signal(s) from the P2X7 receptor activates the XK‐VPS13A complex to scramble phospholipids, followed by necrotic cell death. P2X7 is expressed highly in CD25+CD4+ T cells but weakly in CD8+ (...) T cells, suggesting a role of this system in the activation of the immune system to prevent infection. On the other hand, a loss‐of‐function mutation in XK or VPS13A causes neuroacanthocytosis, indicating the crucial involvement of XK‐VPS13A‐mediated phospholipid scrambling at plasma membranes in the maintenance of homeostasis in the nervous and red blood cell systems. (shrink)

One of the earliest structural changes observed in cells in response to many extracellular factors is membrane ruffling: the formation of motile cell surface protrusions containing a meshwork of newly polymerized actin filaments. It is becoming clear that actin reorganization is an integral part of early signal transduction pathways, and that many signalling molecules interact with the actin cytoskeleton. The small GTP‐binding protein Rac is a key regulator of membrane ruffling, and proteins that can regulate Rac activity, such (...) as Bcr, are likely to act on this signalling pathway. In addition, several previously characterized signal transducing molecules are implicated in the membrane‐ruffling response, including Ras, the adaptor protein Grb2, phosphatidyl inositol 3‐kinase, phospholipase A2 and phorbol ester‐responsive proteins. Changes in polyphosphoinositide metabolism and intracellular Ca2+ levels may also play a role. A number of actin‐binding and organizing proteins localize to membrane ruffles and are potential targets for these signal transducing molecules. (shrink)

Tubulin is the ubiquitous protein that makes up the walls of the cytoskeletal elements known as microtubules. These 20 nm diameter cylindrical fibers are the spindle fibers for mitosis, provide the skeletal framework for cellular elongation, constitute the major structural and motile elements of cilia and flagella and probably play a number of other roles in eukaryote cells. In the electron microscope, they are never seen to attach or protrude directly into or on cellular membranes. It was therefore with much (...) skepticism that cell biologists responded to recent claims purporting to show that tubulin is (or can be) a membrane protein. This skepticism comes from a bias based on the generally understood function of cytoskeletal proteins as representing the intracellular ‘bones’ of cells. The traditional thinking was that microtubules may attach to cellular membranes but only via a cross‐linking connecting protein. In recent years, however, an increasing number of workers have come to believe that tubulin can exist as a normal membrane protein possibly independent of its role in microtubule function. (shrink)

The myelin basic proteins are a set of peripheral membrane polypeptides which play an essential role in myelination. Their most well‐documented property is the unique ability to ‘seal’ the cytoplasmic aspects of the myelin membrane, but this is probably not the only function for these highly charged molecules. Despite extensive homology, the individual myelin basic proteins (MBPs) exhibit different expression patterns and biochemical properties, and so it is now believed that the various isoforms are not functionally equivalent in (...) myelinating cells. We now think that while the major MBPs are intracellular adhesion molecules, some of the quantitatively less abundant isoforms that are expressed very early in development may have regulatory effects on the myelination program. (shrink)

Cell membranes are now emerging as finely tuned molecular systems, signifying that re‐evaluation of our understanding of their structure is essential. Although the idea that cell membrane lipid bilayers do little more than give shape and form to cells and limit diffusion between cells and their environment is totally passé, the structural, compositional, and functional complexity of lipid bilayers often catches cell and molecular biologists by surprise. Models of lipid bilayer structure have developed considerably since the heyday of the (...) fluid mosaic model, principally by the discovery of the restricted diffusion of membrane proteins and lipids within the plane of the bilayer. In reviewing this field, we now suggest that further refinement of current models is necessary and propose that describing lipid bilayers as “finely‐tuned molecular assemblies” best portrays their complexity and function. Also see the video abstract here: https://www.youtube.com/watch?v=ddkP-QRZTl8. (shrink)

A tight control of intracellular [Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document}] is essential for the survival and normal function of cells. In this study we investigate key mechanistic steps by which calcium is regulated and calcium oscillations could occur using in silico modeling of membrane transporters. To do so we give a deterministic description of intracellular Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document} dynamics using nonlinear dynamics in order to understand Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} (...) \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document} signaling. We first present the ordinary differential equations system for cell calcium kinetics and make a preliminary work on Sobol indices. We then describe and analyze complex transporters action. Besides, we analyze the whole system. We finally perform numerical simulations and compare our results to real data. (shrink)

In nature, cells face a variety of stresses that cause physical damage to the plasma membrane and cell wall. It is well established that evolutionarily conserved cell cycle checkpoints monitor various cellular perturbations, including DNA damage and spindle misalignment. However, the ability of these cell cycle checkpoints to sense a damaged plasma membrane/cell wall is poorly understood. To the best of our knowledge, our recent paper described the first example of such a checkpoint, using budding yeast as a (...) model. In this review, we will discuss this important question as well as provide hypothetical explanations to be tested in the future. (shrink)

In recent years, membrane contact sites (MCS), which mediate interactions between virtually all subcellular organelles, have been extensively characterized and shown to be essential for intracellular communication. In this review essay, we focus on an emerging topic: the regulation of MCS. Focusing on the tether proteins themselves, we discuss some of the known mechanisms which can control organelle tethering events and identify apparent common regulatory hubs, such as the VAP interface at the endoplasmic reticulum (ER). We also highlight several (...) currently hypothetical concepts, including the idea of tether oligomerization and redox regulation playing a role in MCS formation. We identify gaps in our current understanding, such as the identity of the majority of kinases/phosphatases involved in tether modification and conclude that a holistic approach—incorporating the formation of multiple MCS, regulated by interconnected regulatory modulators—may be required to fully appreciate the true complexity of these fascinating intracellular communication systems. (shrink)

This article discusses the ascetic–eschatological dimension of consecrated life through the lens of death. Death is not understood as an impenetrable border which separates the two worlds but as a fluid cell membrane which binds time and eternity. The phenomenon of death in consecrated life is perceived in three ritual events: baptism, religious consecration and physical death. These three moments make the so–called 3D transformation which is not only in these three events but through asceticism it is extended to (...) the whole existence of the consecrated person. Ascetic way of living is the membrane where eschaton transcends its own borders. The effort of asceticism and joy of eschaton in consecrated life are two sides of the same reality. Considering the relation between asceticism and eschaton, a convent could be named a heavenly embassy and consecrated people heavenly ambassadors. (shrink)