title: alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering.
abstract: AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that α-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. α-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the rapsyn-α-actinin interaction is increased by agrin, a factor known to stimulate AChR clustering. Downregulation of α-actinin expression inhibits agrin-mediated AChR clustering. Furthermore, the rapsyn-α-actinin interaction can be disrupted by inhibiting Abl and by cholinergic stimulation. Together these results indicate a role for α-actinin in AChR clustering.
authors.affiliation: Institute of Molecular Medicine and Genetics, Department of Neurobiology, Medical College of Georgia, Augusta, Georgia 30912, USA. gclemd@uab.edu
authors.forename: G Clement
authors.initials: GC
authors.lastname: Dobbins
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.forename: Wen C
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000185:Actinin / Q000378:metabolism*; D018171:Agrin / Q000494:pharmacology*; D000818:Animals; D016000:Cluster Analysis; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: C498529:Actn2 protein, mouse; D018171:Agrin; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C051609:peripheral membrane protein 43K; D000185:Actinin