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First published online 13 February 2007
doi: 10.1242/jcs.03367

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

Christi A. Weston^1,2,*, Getu Teressa^1,2, Benjamin S. Weeks³ and Joav Prives^1,

¹ Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA
² Medical Scientist Training Program, Stony Brook University, Stony Brook, NY 11794, USA
³ Department of Biology, Adelphi University, Garden City, NY 11530, USA

Author for correspondence (e-mail: joav{at}pharm.stonybrook.edu)

Accepted 1 December 2006

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.

Key words: Neuromuscular junction, Acetylcholine receptors, Laminin, Agrin, Rho GTPases

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