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- Title
Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway.
- Authors
Kumari, Sudha; Borroni, Virginia; Chaudhry, Ashutosh; Chanda, Baron; Massol, Ramiro; Barrantes, Francisco J.; Mayor, Satyajit
- Abstract
Endocytosis of the nicotinic acetylcholine receptor (AChR) is a proposed major mechanism of neuro-modulation at neuromuscular junctions and in the pathology of synapses in the central nervous system. We show that binding of the competitive antagonist α--bungaro-toxin (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.
- Subjects
ENDOCYTOSIS; NICOTINIC receptors; CHOLINERGIC receptors; SYNAPSES; MYONEURAL junction
- Publication
Journal of Cell Biology, 2008, Vol 181, Issue 7, p1179
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200709086