Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway

Kumari, Sudha ; Borroni, Virginia ; Chaudhry, Ashutosh ; Chanda, Baron ; Massol, Ramiro ; Mayor, Satyajit ; Barrantes, Francisco J. (2008) Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway Journal of Cell Biology, 181 (7). pp. 1179-1193. ISSN 0021-9525

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Official URL: http://jcb.rupress.org/content/181/7/1179.abstract...

Related URL: http://dx.doi.org/10.1083/jcb.200709086

Abstract

Endocytosis of the nicotinic acetylcholine receptor (AChR) is a proposed major mechanism of neuromodulation at neuromuscular junctions and in the pathology of synapses in the central nervous system. We show that binding of the competitive antagonist a-bungarotoxin (αBTX) or antibody-mediated cross-linking induces the internalization of cell surface AChR to late endosomes when expressed heterologously in Chinese hamster ovary cells or endogenously in C2C12 myocytes. Internalization occurs via sequestration of AChR-αBTX complexes in narrow, tubular, surface-connected compartments, which are indicated by differential surface accessibility of fluorescently tagged αBTX-AChR complexes to small and large molecules and real-time total internal reflection fluorescence imaging. Internalization occurs in the absence of clathrin, caveolin, or dynamin but requires actin polymerization. αBTX binding triggers c-Src phosphorylation and subsequently activates the Rho guanosine triphosphatase Rac1. Consequently, inhibition of c-Src kinase activity, Rac1 activity, or actin polymerization inhibits internalization via this unusual endocytic mechanism. This pathway may regulate AChR levels at ligand-gated synapses and in pathological conditions such as the autoimmune disease myasthenia gravis.

Item Type:Article
Source:Copyright of this article belongs to Rockefeller University Press.
ID Code:26709
Deposited On:08 Dec 2010 13:21
Last Modified:17 May 2016 10:00

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