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Int. J. Mol. Sci. 2018, 19(2), 490; https://doi.org/10.3390/ijms19020490

Fundamental Molecules and Mechanisms for Forming and Maintaining Neuromuscular Synapses

1
Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, 540 First Avenue, New York, NY 10011, USA
2
Departments of Neurology and Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Zuckerman Mind Brain Behavior Institute, Columbia University, 3227 Broadway, New York, NY 10027, USA
*
Author to whom correspondence should be addressed.
Received: 9 January 2018 / Revised: 24 January 2018 / Accepted: 29 January 2018 / Published: 6 February 2018
(This article belongs to the Special Issue The Neuromuscular Synapse in Health and Disease)
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Abstract

The neuromuscular synapse is a relatively large synapse with hundreds of active zones in presynaptic motor nerve terminals and more than ten million acetylcholine receptors (AChRs) in the postsynaptic membrane. The enrichment of proteins in presynaptic and postsynaptic membranes ensures a rapid, robust, and reliable synaptic transmission. Over fifty years ago, classic studies of the neuromuscular synapse led to a comprehensive understanding of how a synapse looks and works, but these landmark studies did not reveal the molecular mechanisms responsible for building and maintaining a synapse. During the past two-dozen years, the critical molecular players, responsible for assembling the specialized postsynaptic membrane and regulating nerve terminal differentiation, have begun to be identified and their mechanism of action better understood. Here, we describe and discuss five of these key molecular players, paying heed to their discovery as well as describing their currently understood mechanisms of action. In addition, we discuss the important gaps that remain to better understand how these proteins act to control synaptic differentiation and maintenance. View Full-Text
Keywords: Agrin; Lrp4; MuSK; Dok-7; Rapsyn; Acetylcholine receptors; motor neurons; ALS; congenital myasthenia; myasthenia gravis Agrin; Lrp4; MuSK; Dok-7; Rapsyn; Acetylcholine receptors; motor neurons; ALS; congenital myasthenia; myasthenia gravis
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Burden, S.J.; Huijbers, M.G.; Remedio, L. Fundamental Molecules and Mechanisms for Forming and Maintaining Neuromuscular Synapses. Int. J. Mol. Sci. 2018, 19, 490.

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