INVESTIGADORES
BAIER Carlos Javier
artículos
Título:
Sphingolipids are necessary for nicotinic acetylcholine receptor export in the early secretory pathway
Autor/es:
BAIER CJ; BARRANTES FJ
Revista:
JOURNAL OF NEUROCHEMISTRY
Referencias:
Año: 2007 vol. 101 p. 1072 - 1084
ISSN:
0022-3042
Resumen:
The nicotinic acetylcholine receptor (AChR) is the prototype
ligand-gated ion channel, and its function is dependent on its lipid
environment. In order to study the involvement of sphingolipids (SL) in
AChR trafficking, we used pharmacological approaches to dissect the SL
biosynthetic pathway in CHO-K1/A5 cells heterologously expressing the
muscle-type AChR. When SL biosynthesis was impaired, the cell surface
targeting of AChR diminished with a concomitant increase in the
intracellular receptor pool. The SL-inhibiting drugs increased
unassembled AChR forms, which were retained at the endoplasmic
reticulum (ER). These effects on AChR biogenesis and trafficking could
be reversed by the addition of exogenous SL, such as sphingomyelin. On
the basis of these effects we propose a 'chaperone-like' SL
intervention at early stages of the AChR biosynthetic pathway,
affecting both the efficiency of the assembly process and subsequent
receptor trafficking to the cell surface.