INVESTIGADORES
BARRANTES Francisco Jose
artículos
Título:
Dialogue between membrane lipids and acetylcholine receptor
Autor/es:
BARRANTES, F.J.
Revista:
CURRENT SCIENCE
Editorial:
INDIAN ACAD SCIENCES
Referencias:
Lugar: Bangalore ; Año: 2008 vol. 95 p. 1150 - 1164
ISSN:
0011-3891
Resumen:
The nicotinic acetylcholine receptor (AChR) is the archetype
molecule in the superfamily of Cys-looped ligandgated
ion channels. Members of this superfamily mediate
fast intercellular communication in response to
endogenous neurotransmitters. This review focuses on
structural and functional crosstalk between the AChR
and the lipids in its membrane microenvironment. Influence
on receptor properties is mainly exerted by the
AChR-vicinal (?shell?, ?boundary? or ?annular?) lipids,
which occur in the liquid-ordered phase as opposed to
the more disordered and ?fluid? bulk membrane lipids.
Changes in Förster?s energy transfer (FRET) efficiency
induced by fatty acids, phospholipids and cholesterol
have led to the identification of discrete sites
for these lipids on the AChR protein. Electron-spin
resonance spectroscopy has established the stoichiometry
and selectivity of the shell lipid for the AChR
and disclosed lipid sites in the AChR transmembrane
region. Combined single-channel and site-directed
mutagenesis data fostered the recognition of lipidsensitive
residues in the transmembrane region, dissecting
their contribution to ligand binding and channel
gating, opening and closing. Experimental evidence
supports the notion that the interface between the protein
moiety and the adjacent lipid shell is the locus of
a variety of pharmacologically relevant processes, including
the action of steroids and other lipids.
ABSTRACT
The nicotinic acetylcholine receptor (AChR) is the archetype molecule in the superfamily of Cys-looped ligandgated ion channels. Members of this superfamily mediate fast intercellular communication in response to endogenous neurotransmitters. This review focuses on structural and functional crosstalk between the AchR and the lipids in its membrane microenvironment. Influence on receptor properties is mainly exerted by the AChR-vicinal (?shell?, ?boundary? or ?annular?) lipids, which occur in the liquid-ordered phase as opposed to the more disordered and ?fluid? bulk membrane lipids. Changes in Förster?s energy transfer (FRET) efficiency induced by fatty acids, phospholipids and cholesterol have led to the identification of discrete sites for these lipids on the AChR protein. Electron-spin resonance spectroscopy has established the stoichiometry and selectivity of the shell lipid for the AchR and disclosed lipid sites in the AChR transmembrane region. Combined single-channel and site-directed mutagenesis data fostered the recognition of lipid-sensitive residues in the transmembrane region, dissecting their contribution to ligand binding and channel gating, opening and closing. Experimental evidence supports the notion that the interface between the protein moiety and the adjacent lipid shell is the locus of a variety of pharmacologically relevant processes, including the action of steroids and other lipids.
Keywords: Acetylcholine receptor, membrane lipids, protein moiety, protein-vicinal lipid.