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Publication : Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways.

First Author  Weston CA Year  2007
Journal  J Cell Sci Volume  120
Issue  Pt 5 Pages  868-75
PubMed ID  17298982 Mgi Jnum  J:120754
Mgi Id  MGI:3707929 Doi  10.1242/jcs.03367
Citation  Weston CA, et al. (2007) Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways. J Cell Sci 120(Pt 5):868-75
abstractText  During neuromuscular junction formation, extracellular matrix-mediated signals cause muscle surface acetylcholine receptors (AChRs) to aggregate at synaptic sites. Two extracellular matrix proteins, agrin and laminin, have each been shown to initiate signaling pathways that culminate in AChR clustering in cultured muscle cells. Here we present evidence that laminin-induced AChR clustering is mediated by the activation of the Rho GTPases Cdc42, Rac and Rho. Clustering in response to laminin is blocked by the dominant negative mutants Cdc42N17, RacN17 and RhoN19, as well as by the Rho inhibitor C3 transferase. Moreover, laminin-induced AChR clustering is impaired by the Rho kinase inhibitor Y-27632. Agrin-induced AChR clustering has previously been shown to require activation of Cdc42, Rac and Rho. Therefore, although agrin and laminin use distinct transmembrane receptors to initiate AChR clustering, their signaling pathways converge at the level of Rho GTPase activation.
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