Browsing Institute of Molecular Medicine and Genetics: Faculty Research and Presentations by Authors
alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering.Dobbins, G Clement; Luo, Shiwen; Yang, Zhihua; Xiong, Wen C; Mei, Lin; Institute of Molecular Medicine and Genetics; Department of Neuroscience and Regenerative Medicine (2009-01-13): AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that alpha-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. alpha-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the rapsyn-alpha-actinin interaction is increased by agrin, a factor known to stimulate AChR clustering. Downregulation of alpha-actinin expression inhibits agrin-mediated AChR clustering. Furthermore, the rapsyn-alpha-actinin interaction can be disrupted by inhibiting Abl and by cholinergic stimulation. Together these results indicate a role for alpha-actinin in AChR clustering.