The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the level (...) of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

AbstractmRNA stability is increasingly recognized as being essential for controlling the expression of a wide variety of transcripts during neuronal development and synaptic plasticity. In this context, the role of AU‐rich elements (ARE) contained within the 3′ untranslated region (UTR) of transcripts has now emerged as key because of their high incidence in a large number of cellular mRNAs. This important regulatory element is known to significantly modulate the longevity of mRNAs by interacting with available stabilizing or destabilizing RNA‐binding proteins (...) (RBP). Thus, in parallel with the emergence of ARE, RBP are also gaining recognition for their pivotal role in regulating expression of a variety of mRNAs. In the nervous system, the member of the Hu family of ARE‐binding proteins known as HuD, has recently been implicated in multiple aspects of neuronal function including the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. Through its ability to interact with ARE and stabilize multiple transcripts, HuD has now emerged as an important regulator of mRNA expression in neurons. The present review is designed to provide a comprehensive and updated view of HuD as an RBP in the nervous system. Additionally, we highlight the role of HuD in multiple aspects of a neuron's life from early differentiation to changes in mature neurons during learning paradigms and in response to injury and regeneration. Finally, we describe the current state of knowledge concerning the molecular and cellular events regulating the expression and activity of HuD in neurons. BioEssays 28: 822–833, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic ‘knockout’ experiments(1,2), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology(3). In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular (...) synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse‐specific expression to the utrophin gene(4,5). Identification of the events culminating in the transaction of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD. (shrink)