INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
artículos
Título:
Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway.
Autor/es:
KUMARI S; BORRONI V; CHAUDHRY A; CHANDA B; MASSOL R; MAYOR S,; BARRANTES FJ
Revista:
JOURNAL OF CELL BIOLOGY
Editorial:
The Rockefeller University Press
Referencias:
Año: 2008 p. 1179 - 1193
ISSN:
0021-9525
Resumen:
Kumari, S., Borroni, V., Chaudhry, A., Chanda, B., Massol, R., Mayor, S. y Barrantes, F.J. (2008). Nicotinic acetylcholine receptor is internalized via a Rac-dependent dynamin-independent endocytic pathway. J. Cell Biol. 181, 1179-1193.
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 alpha-bungarotoxin (alphaBTX) 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 alphaBTX complexes in narrow, tubular, surface-connected compartments, which are indicated by differential surface accessibility of fluorescently tagged alphaBTX AChR complexes to small and large
molecules and real-time total internal refl ection fl uorescence imaging. Internalization occurs in the absence of clathrin, caveolin, or dynamin but requires actin polymerization. AlphaBTX 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.