Sorbs1 and -2 Interact with CrkL and Are Required for Acetylcholine Receptor Cluster Formation.
Sorbs1 and -2 Interact with CrkL and Are Required for Acetylcholine Receptor Cluster Formation.
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DOI：
10.1128/mcb.00775-15
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发表时间：
2016-01-15
影响因子：
5.3
通讯作者：
Glass DJ
中科院分区：
文献类型：
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作者：
Hallock PT;Chin S;Blais S;Neubert TA;Glass DJ
Crk和CrkL是形成神经肌肉突触所必需的非催化接头蛋白，其作用于肌肉特异性激酶（MuSK）的下游，MuSK是骨骼肌中表达的受体酪氨酸激酶，以及MuSK结合蛋白Dok-7。Crk/CrkL如何调节神经肌肉终板形成尚不清楚。为了更好地了解Crk/CrkL的作用，我们使用质谱法鉴定了CrkL结合蛋白，并鉴定出Sorbs1和Sorbs2是两个功能冗余蛋白，它们与启动MuSK/Dok-7/Crk/CrkL复合物相关，在体外调节乙酰胆碱受体（AChR）聚类，并且在体内定位于突触。
Crk and CrkL are noncatalytic adaptor proteins necessary for the formation of neuromuscular synapses which function downstream of muscle-specific kinase (MuSK), a receptor tyrosine kinase expressed in skeletal muscle, and the MuSK binding protein Dok-7. How Crk/CrkL regulate neuromuscular endplate formation is not known. To better understand the roles of Crk/CrkL, we identified CrkL binding proteins using mass spectrometry and have identified Sorbs1 and Sorbs2 as two functionally redundant proteins that associate with the initiating MuSK/Dok-7/Crk/CrkL complex, regulate acetylcholine receptor (AChR) clustering in vitro, and are localized at synapses in vivo.