Vezatin is required for the maturation of the neuromuscular synapse

Mol Biol Cell. 2019 Sep 15;30(20):2571-2583. doi: 10.1091/mbc.E19-06-0313. Epub 2019 Aug 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Cell Line
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout
  • Muscle Proteins / metabolism
  • Neuromuscular Junction / embryology*
  • Neuromuscular Junction / genetics*
  • Neuromuscular Junction / metabolism
  • Phosphorylation
  • Receptors, Nicotinic / metabolism
  • Synapses / metabolism


  • Agrin
  • Carrier Proteins
  • Membrane Proteins
  • Muscle Proteins
  • Receptors, Nicotinic
  • peripheral membrane protein 43K
  • vezatin protein, mouse