Hallock_2010_Genes.Dev_24_2451

Reference

Title : Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L - Hallock_2010_Genes.Dev_24_2451
Author(s) : Hallock PT , Xu CF , Park TJ , Neubert TA , Curran T , Burden SJ
Ref : Genes Dev , 24 :2451 , 2010
Abstract :

Agrin, released by motor neurons, promotes neuromuscular synapse formation by stimulating MuSK, a receptor tyrosine kinase expressed in skeletal muscle. Phosphorylated MuSK recruits docking protein-7 (Dok-7), an adaptor protein that is expressed selectively in muscle. In the absence of Dok-7, neuromuscular synapses fail to form, and mutations that impair Dok-7 are a major cause of congenital myasthenia in humans. How Dok-7 stimulates synaptic differentiation is poorly understood. Once recruited to MuSK, Dok-7 directly stimulates MuSK kinase activity. This unusual activity of an adapter protein is mediated by the N-terminal region of Dok-7, whereas most mutations that cause congenital myasthenia truncate the C-terminal domain. Here, we demonstrate that Dok-7 also functions downstream from MuSK, and we identify the proteins that are recruited to the C-terminal domain of Dok-7. We show that Agrin stimulates phosphorylation of two tyrosine residues in the C-terminal domain of Dok-7, which leads to recruitment of two adapter proteins: Crk and Crk-L. Furthermore, we show that selective inactivation of Crk and Crk-L in skeletal muscle leads to severe defects in neuromuscular synapses in vivo, revealing a critical role for Crk and Crk-L downstream from Dok-7 in presynaptic and postsynaptic differentiation.

PubMedSearch : Hallock_2010_Genes.Dev_24_2451
PubMedID: 21041412

Related information

Citations formats

Hallock PT, Xu CF, Park TJ, Neubert TA, Curran T, Burden SJ (2010)
Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L
Genes Dev 24 :2451

Hallock PT, Xu CF, Park TJ, Neubert TA, Curran T, Burden SJ (2010)
Genes Dev 24 :2451