Specific extracellular interaction between glycophosphatidylinositol (GPI)‐anchored proteins and adhesion G protein‐coupled receptors (aGPCRs) plays an important role in unique biological functions. GPI‐anchored proteins are derived from a novel post‐translational modification of single‐span membrane molecules, while aGPCRs are bona fide seven‐span transmembrane proteins with a long extracellular domain. Although various members of the two structurally‐distinct protein families are known to be involved in a wide range of biological processes, many remain as orphans. Interestingly, accumulating evidence has pointed to a complex (...) interaction and functional synergy between these two protein families. I discuss herein current understanding of specific functional partnerships between GPI‐anchored proteins and aGPCRs. (shrink)

The Economy for the Common Good proposes a more ethical and sustainable society and organizations based on the common good concept. The study investigates entrepreneurs' reasons for joining the ECG movement and organizational changes introduced following the implementation of the ECG managerial system. Semistructured interviews were held with managers of nine Italian organizations belonging to the movement. Interviews were transcribed, and qualitative content analysis was performed using NVivo 12. Eleven nodes integrating 279 answer units were coded, addressing reasons for adhering, (...) actions introduced, difficulties, overcoming strategies and enablers. The results suggest that ECG values and particularly Environmental Sustainability and Human Dignity are two main reasons to join the movement, that a Common Good Report is a valuable tool for the organizational analysis, that such analysis can be replicated with other ECG organizations, and that pursuing decent work conditions strengthens the adhesion to the ECG movement. The seven conceptual propositions highlight the congruence between the value structure of the organization and the values of the ECG, the congruence between the values held by proximal organizational stakeholders and the changes encouraged by ECG approach, and that rewards and recognition by the organizational stakeholders and society reinforce and maintain the adhesion path. (shrink)

Les croyances ont une face subjective – elles existent parmi les états mentaux d’un agent éventuellement rationnel – et une face objective : avoir une croyance est essentiellement pour l’agent représenter quelque chose comme existant dans son environnement ou, s’il dispose d’un tel concept, représenter un contenu comme vrai. La relation des deux faces de la croyance a été souvent envisagée dans la littérature, donnant lieu à différents slogans plus ou moins heureux, par exemple que la croyance vise le vrai, (...) ou que le vrai est la norme de la croyance et de l’assertion. La lecture du texte de Gil sur la conviction suggère de reconsidérer cette relation et d’isoler un élément de la croyance, que j’appelle adhésion, qui lui-même se décline sous deux aspects, tenir pour vrai et tenir pour sien. Cette adhésion n’est ni identique ni réductible à l’acquiescement (section 2). Elle a sa phénoménologie propre (section 3) et est profondément bidimensionnelle (section 4). Elle est idéalement, c’est-à-dire seulement dans certaines situations de rationalité forte, une fonction de la justification (section 5). Enfin et surtout : elle doit être envisagée en combinant le profil modal du contenu de la croyance et le profil modal de l’élément attitudinal, c’est-à-dire du mode intentionnel (section 6). (shrink)

There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell–cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic changes in (...) the organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. (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)

G protein‐coupled receptors (GPCRs) constitute the largest family of transmembrane proteins and play a crucial role in regulating diverse cellular functions. They transmit their signaling via binding to intracellular signal transducers and effectors, such as G proteins, GPCR kinases, and β‐arrestins. To influence specific GPCR signaling behaviors, β‐arrestins recruit effectors to form larger signaling complexes. Intriguingly, they facilitate divergent functions for the binding to different receptors. Recent studies relying on advanced structural approaches, novel biosensors and interactome analyses bring (...) us closer to understanding how this specificity is achieved. In this article, we share our hypothesis of how active GPCRs induce specific conformational rearrangements within β‐arrestins to reveal distinct binding interfaces, enabling the recruitment of a subset of effectors to foster specialized signaling complexes. Furthermore, we discuss methods of how to comprehensively assess β‐arrestin conformational states and present the current state of research regarding the functionality of these multifaceted scaffolding proteins. (shrink)

This book examines the most controversial issues concerning the use of pre-drafted clauses in fine print, which are usually included in consumer contracts and presented to consumers on a take-it-or-leave-it basis. By applying a multi-disciplinary approach that combines consumer's psychology and seller's drafting power in the logic of efficiency and good faith, the book provides a fresh and unconventional analysis of the existing literature, both theoretical and empirical. Moving from the unconscionability doctrine, it criticizes (and in some cases refutes) its (...) main conclusions based on criteria which are usually invoked to sustain the need for public intervention to protect consumers, and specifically related to Law (contract complexity), Psychology (consumer lack of sophistication criterion) and Economics (market structure criterion). It also analyzes the effects of different regulations, such as banning vexatious clauses or mandating disclosure clauses, showing that none of them protect consumers, but in fact prove to be harmful when consumers are more vulnerable, that is whenever sellers can exploit some degree of market power. In closing, the book combines these disparate aspects, arguing that the solution (if any) to the problem of consumer exploitation and market inefficiency associated with the use of contracts of adhesion in these contexts cannot be found in removing or prohibiting hidden clauses, but instead has to take into account the effects of these clauses on the contract as a whole. (shrink)

Physical forces regulate numerous biological processes during development, physiology, and pathology. Forces between the external environment and intracellular actin cytoskeleton are primarily transmitted through integrin‐containing focal adhesions and cadherin‐containing adherens junctions. Crosstalk between these complexes is well established and modulates the mechanical landscape of the cell. However, integrins and cadherins constitute large families of adhesion receptors and form multiple complexes by interacting with different ligands, adaptor proteins, and cytoskeletal filaments. Recent findings indicate that integrin‐containing hemidesmosomes oppose force transduction and (...) traction force generation by focal adhesions. The cytolinker plectin mediates this crosstalk by coupling intermediate filaments to the actin cytoskeleton. Similarly, cadherins in desmosomes might modulate force generation by adherens junctions. Moreover, mechanotransduction can be influenced by podosomes, clathrin lattices, and tetraspanin‐enriched microdomains. This review discusses mechanotransduction by multiple integrin‐ and cadherin‐based cell adhesion complexes, which together with the associated cytoskeleton form an integrated network that allows cells to sense, process, and respond to their physical environment. (shrink)

Focal adhesion kinase (FAK) is a nonreceptor protein‐tyrosine kinase implicated in controlling cellular responses to the engagement of cell‐surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v‐Src. Progress toward elucidating the events leading to FAK activation following integrin‐mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership (...) is formed between FAK and Src‐family kinases, leading to tyrosine phosphorylation of FAK and associated ‘docking’ proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c‐Crk, to the complex is likely to trigger adhesion‐induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras‐MAP kinase pathway. (shrink)

As in other Latin American countries, Muslim presence in Argentina traces its origin to Arab migration waves in the late nineteenth and early twentieth century; most of these immigrants came from Lebanon and Syria. We can identify three historical periods; each of these stages involves different degrees of institutionalization, diversification, visibility and negotiation of recognition in the national arena. Currently, Islam is one of the religious options available in a plural religious field and, increasingly, the communities are composed of Muslim (...) Arab descendants and converts. This paper analyze the adhesion to Islam as a dynamic process that includes conversion, tradition, return to religion and intra-Islamic transit among Muslim descendants. Using an ethnographic approach I will examine individual trajectories of converts and Muslim descendants, on the basis of these analyses I will try to establish a critical dialogue with the literature on conversion to Islam. This article also problematizes the converts/Muslim descendants’ dichotomy in order to arrive at a more comprehensive understanding of the dynamic of adhesion to Islam. (shrink)

G protein‐coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β‐arrestins. Many agonists of GPCRs promote “biased” responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential “hidden variables” that regulate this behavior. One contributor is “location bias,” which refers to the generation of unique signaling cascades from a given GPCR depending upon (...) the cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias. (shrink)

Neural cell adhesion molecules of the immunoglobulin superfamily are important components of the network of guidance cues and receptors that govern axon growth and guidance during development. For neural cell adhesion molecule L1, the combined application of human genetics, knockout mouse technology, and cell biology is providing fundamental insight into the role of L1 in mediating neuronal differentiation. Disease-causing mutations as well as mouse models of L1 disruption can now be used to examine the relevance of L1 binding (...) specificities and signal transduction pathways that have been observed in vitro. BioEssays 20:668–675, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Neural cell adhesion molecules of the immunoglobulin superfamily are important components of the network of guidance cues and receptors that govern axon growth and guidance during development. For neural cell adhesion molecule L1, the combined application of human genetics, knockout mouse technology, and cell biology is providing fundamental insight into the role of L1 in mediating neuronal differentiation. Disease-causing mutations as well as mouse models of L1 disruption can now be used to examine the relevance of L1 binding (...) specificities and signal transduction pathways that have been observed in vitro. BioEssays 20:668–675, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Multicellularity in the cellular slime mold Dictyostelium discoideum is achieved by the expression of two types of cell–cell adhesion sites. The EDTA‐sensitive adhesion sites are expressed very early in the developmental cycle and a surface glycoprotein of 24000 Da is known to be responsible for these sites. The EDTA‐resistant contact sites begin to accumulate on the cell surface at the aggregation stage of development. Several glycoproteins have been implicated in the EDTA‐resistant type of cell–cell binding and the best (...) characterized one has an Mr of 80000 (gp80). gp80 mediates cell–cell binding via homophilic interaction and its cell binding site has been mapped to an octapeptide sequence. The mechanism by which gp80 mediates cell–cell adhesion will be discussed. (shrink)

The recognition of extracellular molecules by cell surface receptors is the principal mechanism used by cells to sense their environment. Consequently, signals transduced as a result of these interactions make a major contribution to the regulation of cellular phenotype. Historically, particular emphasis has been placed on elucidating the intracellular consequences of growth factor and cytokine binding to cells. In addition to these interactions, however, cells are usually in intimate contact with a further source of complex structural and functional information, namely (...) immobilised extracellular matrix and/or cell surface adhesion proteins. A key question in recent years has been whether cells use the myriad of adhesion protein‐receptor interactions purely for structural and migratory function, or whether these interactions also make a more varied contribution to cell phenotype. Here we review dynamic aspects of the function of one major class of adhesion receptor, the integrins. In particular, we focus on the evidence for shape changes in integrin molecules, the mechanisms responsible for regulating ligand binding, and the signals transduced following integrin occupancy. (shrink)

In A Letter Concerning Toleration, John Locke argues in favor of religious toleration positing that the state cannot make a person's life better by forcing that person to live according to beliefs he refuses. More recently, Ronald Dworkin and Will Kymlicka have developed similar arguments. In the first case, against some paternalistic policies; in the second, in support of the liberal ideal of state neutrality. My aim in the present paper is to analyze the plausibility of these arguments conceived as (...) a defense of liberal neutrality. I will prove that both versions of the argument fail. In section II, I will object the argument's capability to support the conclusions it attempts to establish, without raising doubts about the reliability of its premises. In section III, I will submit three objections against the conception of critical well-being that constitutes the core of both versions of the argument. (shrink)

Focal adhesions disassemble during mitosis, but surprisingly little is known about how these structures respond to other phases of the cell cycle. Three recent papers reveal unexpected results as they examine adhesions through the cell cycle. A biphasic response is detected where focal adhesions grow during S phase before disassembly begins early in G2. In M phase, activated integrins at the tips of retraction fibers anchor mitotic cells, but these adhesions lack the defining components of focal adhesions, such as talin, (...) paxillin, and zyxin. Re‐examining cell‐matrix adhesion reveals reticular adhesions, a new class of adhesion. These αVβ5 integrin‐mediated adhesions also lack conventional focal adhesion components and anchor mitotic cells to the extracellular matrix. As reviewed here, these studies present insight into how adhesion complexes vary through the cell cycle, and how unconventional adhesions maintain attachment during mitosis while providing spatial memory to guide daughter cell re‐spreading after cell division. (shrink)

According to process ontology in the philosophy of biology, the living world is better understood as processes rather than as substantial individuals. Within this perspective, an organism does not consist of a hierarchy of structures like a machine, but rather a dynamic hierarchy of processes, dynamically maintained and stabilized at different time scales. With this respect, two processual approaches on enzymes by Stein (Hyle Int J Philos Chem 10(4):5–22, 2004, Process Stud 34:62–80, 2005, Found Chem 8:3–29, 2006) and by Guttinger (...) (Everything Flows: Towards a Processual Philosophy of Biology, Oxford University Press, Oxford, 2018) allows to think of macromolecules as relational and processual entities. In this work, I propose to extend their arguments to another case study within the biochemical domain, which is the case of ligand receptors and receptor-mediated biosignaling. The aim of this work is to analyze the case of G Protein-Coupled Receptors and biosignaling under the consideration of a processual ontology. I will defend that the processual ontology framework is adequate for the biochemical domain and that it allows accounting for the current biochemical knowledge related to the case study. (shrink)

According to process ontology in the philosophy of biology, the living world is better understood as processes rather than as substantial individuals. Within this perspective, an organism does not consist of a hierarchy of structures like a machine, but rather a dynamic hierarchy of processes, dynamically maintained and stabilized at different time scales. With this respect, two processual approaches on enzymes by Stein (Hyle Int J Philos Chem 10(4):5–22, 2004, Process Stud 34:62–80, 2005, Found Chem 8:3–29, 2006) and by Guttinger (...) (Everything Flows: Towards a Processual Philosophy of Biology, Oxford University Press, Oxford, 2018) allows to think of macromolecules as relational and processual entities. In this work, I propose to extend their arguments to another case study within the biochemical domain, which is the case of ligand receptors and receptor-mediated biosignaling. The aim of this work is to analyze the case of G Protein-Coupled Receptors and biosignaling under the consideration of a processual ontology. I will defend that the processual ontology framework is adequate for the biochemical domain and that it allows accounting for the current biochemical knowledge related to the case study. (shrink)

The environmental complexity in which living organisms found themselves throughout evolution, most likely resulted in various encounters that would continuously challenge the organisms' ability to survive. Coping with this stress can prove energetically demanding and might require the proper coupling between mechanisms aimed at sensing external stimuli and cellular strategies geared at producing energy. In this issue of BioEssays, Lovejoy and Hogg hypothesize that preservation of this bifaceted coupling can be detected by the maintenance and evolution of stress response mechanisms (...) at the genomic, molecular and cellular levels. Through ancestry‐tracking, they identify a group of related G protein‐coupled receptor systems with intersecting stress‐modulating properties which might represent an essential part of a complex organism's coping mechanisms to stress, an attribute that they suspect may be affected in individuals suffering from mood disorders such as depression. (shrink)

We have been using feather development as a model for understanding the molecular basis of pattern formation and to explore the roles of homeoproteins, retinoids and adhesion molecules in this process. Two kinds of homeobox (Hox) protein gradients in the skin have been identified: a ‘microgradient’ within a single feather bud and a ‘macrogradient’ across the feather tract. The asynchronous alignment of different Hox macrogradients establishes a unique repertoire of Hox expression patterns in skin appendages within the integument, designated (...) here as the ‘Hox codes of skin appendages’. It is hypothesized that these Hox codes contribute to the phenotypic determination of skin appendages. High doses of retinoic acid cause a morphological transformation between feather and scale, while low doses of retinoic acid cause an alteration of the axial orientation of skin appendages. We have tested the ability of molecules directly involved in the feather formation process to mediate the action of the Hox codes, and surmise that adhesion molecules are potential candidates. Using specific Fabs to suppress the activity of adhesion molecules, we have found that L‐CAM is involved in the formation of the hexagonal pattern, N‐CAM is involved in mediating dermal condensations, tenascin is involved in feather bud growth and elongation, and integrin β‐1 is essential for epithelial‐mesenchymal interactions. More work is in progress to fully understand the molecular pathways regulating the feather formation process. (shrink)

En A Letter Concerning Toleration John Locke argumenta en favor de la tolerancia religiosa afirmando que el Estado no puede mejorar la vida de las personas forzándolas a vivir de acuerdo con creencias que ellas no suscriben. Más recientemente, Ronald Dworkin y Will Kymlicka han desarrollado argumentos similares. En el caso del primero, contra ciertas políticas paternalistas; en el del segundo, en apoyo de la tesis liberal de la neutralidad estatal. Mi propósito en el presente artículo es analizar la plausibilidad (...) de dichos argumentos concebidos como una defensa de la tesis de la neutralidad estatal. Intentaré demostrar que ambas versiones del argumento fracasan. En la sección II, cuestionaré la capacidad de los argumentos para respaldar las conclusiones que aspiran establecer, sin objetar la plausibilidad de las premisas involucradas. En la sección III, desarrollaré tres objeciones contra la concepción del bienestar crítico que constituye el corazón de ambas versiones del argumento. In A Letter Concerning Toleration, John Locke argues in favor of religious toleration positing that the state cannot make a person's life better by forcing that person to live according to beliefs he refuses. More recently, Ronald Dworkin and Will Kymlicka have developed similar arguments. In the first case, against some paternalistic policies; in the second, in support of the liberal ideal of state neutrality. My aim in the present paper is to analyze the plausibility of these arguments conceived as a defense of liberal neutrality. I will prove that both versions of the argument fail. In section II, I will object the argument's capability to support the conclusions it attempts to establish, without raising doubts about the reliability of its premises. In section III, I will submit three objections against the conception of critical well-being that constitutes the core of both versions of the argument. (shrink)

Bidirectional trans‐synaptic signaling is essential for the formation, maturation, and plasticity of synaptic connections. Synaptic cell adhesion molecules (CAMs) are prime drivers in shaping the identities of trans‐synaptic signaling pathways. A series of recent studies provide evidence that diverse presynaptic cell adhesion proteins dictate the regulation of specific synaptic properties in postsynaptic neurons. Focusing on mammalian synaptic CAMs, this article outlines several exemplary cases supporting this notion and highlights how these trans‐synaptic signaling pathways collectively contribute to the specificity (...) and diversity of neural circuit architecture. (shrink)

Some years ago, Hidding et al. suggest that the emergence of intricate and pervasive weblike structure of the Universe on Megaparsec scales can be approximated by a well-known equation from fluid mechanics, the Burgers’ equation. The solution to this equation can be obtained from a geometrical formalism. The resulting Adhesion formalism provides deep insight into the dynamics and topology of the Cosmic Web. It uncovers a direct connection between the conditions in the very early Universe and the complex spatial (...) patterns that emerged out of these under the influence of gravity. In the present paper, we describe a cellular automaton model of the Burgers’ equation, which can be investigated via a fast computer simulation. In the end, this suggests a Cellular Automata Adhesion Model of the Universe. (shrink)

Members of the CAR group of Ig‐like type I transmembrane proteins mediate homotypic cell adhesion, share a common overall extracellular domain structure and are closely related at the amino acid sequence level. CAR proteins are often found at tight junctions and interact with intracellular scaffolding proteins, suggesting that they might modulate tight junction assembly or function. However, impairment of tight junction integrity has not been reported in mouse knockout models or zebrafish mutants of CAR members. In contrast, in the (...) same knockout models deficits in gap junction communication were detected in several organ systems, including the atrioventricular node of the heart, smooth muscle cells of the intestine and the ureter and in Sertoli cells of the testes. Possible interactions between BT‐IgSF and connexin41.8 on the disturbed pattern of pigment stripes found in zebrafish mutants and between ESAM and connexin43 during hematopoiesis in the mouse are also discussed. On the basis of the combined data and phenotypic similarities between CAR member mutants and connexin mutants I hypothesize that they primarily play a role in the organization of gap junction communication. Also see the video abstract here: https://youtu.be/i0yq2KhuDAE. (shrink)

The integrins are receptors for proteins of the extracellular matrix, both providing a physical link to the cytoskeleton and transducing signals from the extracellular matrix. Activation of integrins leads to tyrosine and serine phosphorylation of a number of proteins, elevation of cytosolic calcium levels, cytoplasmic alkalinization, changes in phospholipid metabolism and, ultimately, changes in gene expression. The recently discovered focal adhesion kinase localizes to focal contacts, which are sites of integrin clustering, and focal adhesion kinase can physically associate (...) with integrins in vitro. As integrins lack intrinsic catalytic activity, focal adhesion kinase is a candidate for a signaling molecule that is recruited by integrins in order to trigger the generation of intracellular second messengers. Thus, focal adhesion kinase may play a central role in signal transduction through integrins. (shrink)

During vertebrate limb development, various genes of the Hox family, the products of which influence skeletal element identity, are expressed in specific spatiotemporal patterns in the limb bud mesenchyme. At the same time, the cells also exhibit ‘self‐organizing’ behavior – interacting with each other via extracellular matrix and cell‐cell adhesive molecules to form the arrays of mesenchymal condensations that lead to the cartilaginous skeletal primordia. A recent study by Yokouchi et al.(1) establishes a connection between these phenomena. They misexpressed the (...) product of the Hoxa‐13 gene in chick limb buds and demonstrated both skeletal pattern perturbations and changes in cell‐cell adhesivity in mesenchyme aberrantly expressing this protein. (shrink)

T lymphocyte recognition of foreign antigens and migration throughout the body require the regulated adhesion of lymphocytes to diverse types of cells and to the extracellular matrix. The lymphocyte adhesion ‘receptor’ LFA‐1, a member of the integrin family, interacts with ICAM‐1 and other counter‐receptors to mediate adhesion. The LFA‐1/ICAM‐1 interaction is regulated by signals transmitted from the cytoplasm to the extracellular space. Conversely, LFA‐1 transmits signals from the extracellular space to the cytoplasm to regulate T lymphocyte activation. (...) The observed properties of LFA‐1 and related adhesion ‘receptors’ are incorporated into a general model for adhesion during immune surveillance and recognition of foreign antigens. (shrink)

One of the most important cell–cell interactions is that of the sperm with the egg. This interaction, which begins with cell adhesion and culminates with membrane fusion, is mediated by multiple molecules on the gametes. One of the best-characterized of these molecules is fertilin β, a ligand on mammalian sperm and one of the first ADAMs (A Disintegrin and A Metalloprotease domain) to be identified. Fertilin β (also known as ADAM2) participates in sperm–egg membrane binding, and it has long (...) been hypothesized that this function is achieved through the interaction of the disintegrin domain of fertilin β with an integrin on the egg surface. There are now approximately 30 members of the ADAM family and, to date, five different ADAMs (fertilin β, ADAM9, ADAM12, ADAM15, ADAM23) have been described to interact with integrins (specifically α6β1, αvβ3, α9β1, αvβ5, and/or α5β1). This field will be discussed with respect to what is known about specific ADAMs and the integrins with which they interact, and what the implications are for sperm–egg interactions and for integrin function. These data will also be discussed in the context of recent knockout studies, which show that eggs lacking the α6 integrin subunit can be fertilized, and eggs lacking the integrin-associated tetraspanin protein CD9 fail to fertilize. Key issues in cell adhesion that pertain to gametes and fertilization will also be highlighted. BioEssays 23:628–639, 2001. © 2001 John Wiley & Sons, Inc. (shrink)