Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 30, Issue 20, Pages 2571-2583Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E19-06-0313
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Funding
- National Institutes of Health [RO1 NS-075124, P30 NS050276]
- National Research Service Award (NRSA) predoctoral fellowship
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Key genes, such as Agrin, Lrp4, and MuSK, are required for the initial formation, subsequent maturation, and long-term stabilization of mammalian neuromuscular synapses. Additional molecules are thought to function selectively during the evolution and stabilization of these synapses, but these molecular players are largely unknown. Here, we used mass spectrometry to identify vezatin, a two-pass transmembrane protein, as an acetylcholine receptor (AChR)-associated protein, and we provide evidence that vezatin binds directly to AChRs. We show that vezatin is dispensable for the formation of synapses but plays a later role in the emergence of a topologically complex and branched shape of the synapse, as well as the stabilization of AChRs. In addition, neuromuscular synapses in vezatin mutant mice display premature signs of deterioration, normally found only during aging. Thus, vezatin has a selective role in the structural elaboration and postnatal maturation of murine neuromuscular synapses.
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