Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016.
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 , , and , 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 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.
关键基因，如 、 、和 ，对于哺乳动物神经肌肉突触的初始形成、随后的成熟和长期稳定是必需的。人们认为，在这些突触的进化和稳定过程中，还有其他分子选择性地发挥作用，但这些分子参与者在很大程度上是未知的。在这里，我们使用质谱法鉴定出 vezatin，一种具有两个跨膜结构域的跨膜蛋白，是乙酰胆碱受体 (AChR) 相关蛋白，并提供了 vezatin 直接结合 AChR 的证据。我们表明 vezatin 对于突触的形成不是必需的，但在突触拓扑结构的复杂性和分支形状的出现以及 AChR 的稳定中发挥后期作用。此外，在 突变小鼠的神经肌肉突触中显示出退化的早期迹象，这些迹象通常只在衰老过程中出现。因此，vezatin 在小鼠神经肌肉突触的结构细化和出生后成熟过程中具有选择性作用。
