Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Channels (Austin)
2008 Jan 01;23:180-90. doi: 10.4161/chan.2.3.6155.
Show Gene links
Show Anatomy links
Potential role of caveolin-1-positive domains in the regulation of the acetylcholine receptor's activatable pool: implications in the pathogenesis of a novel congenital myasthenic syndrome.
Báez-Pagán CA
,
Martínez-Ortiz Y
,
Otero-Cruz JD
,
Salgado-Villanueva IK
,
Velázquez G
,
Ortiz-Acevedo A
,
Quesada O
,
Silva WI
,
Lasalde-Dominicci JA
.
???displayArticle.abstract???
Cholesterol modulates the plasmalemma's biophysical properties and influences the function and trafficking of membrane proteins. A fundamental phenomenon that remains obscure is how the plasmalemma's lipid composition regulates the activatable pool of membrane receptors. An outstanding model to study this phenomenon is the nicotinic acetylcholine receptor (nAChR), since the nAChR activatable pool has been estimated to be but a small fraction of the receptors present in the plasmalemma. Studies on the effect of cholesterol depletion in the function of the Torpedo californica nAChR, using the lipid-exposed nAChR mutation (alpha C418W) that produces a congenital myasthenic syndrome (CMS), demonstrated that cholesterol depletion causes a remarkable increase in the alpha C418W nAChR's macroscopic current whereas not in the wild-type (WT). A variety of approaches were used to define the mechanism responsible for the cholesterol depletion mediated-increase in the alpha C418W nAChR's macroscopic current. The present study suggests that a substantial fraction of the alpha C418W nAChRs is located in caveolin-1-positive domains, "trapped" in a non-activatable state, and that membrane cholesterol depletion results in the relocation of these receptors to the activatable pool. Co-fractionation and co-immunoprecipitation of the alpha C418W nAChR and the membrane raft protein caveolin-1 (cav1) support the notion that interactions at lipid-exposed domains regulate the partition of the receptor into membrane raft microdomains. These results have potential implications as a novel mechanism to fine-tune cholinergic transmission in the nervous system and in the pathogenesis associated to the alpha C418W nAChR.
Albuquerque,
The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates.
1974, Pubmed
Albuquerque,
The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates.
1974,
Pubmed
Anderson,
Calorimetric measurement of phospholipid interaction with methyl-beta-cyclodextrin.
2004,
Pubmed
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Blanton,
Mapping the lipid-exposed regions in the Torpedo californica nicotinic acetylcholine receptor.
1992,
Pubmed
Blanton,
Identifying the lipid-protein interface of the Torpedo nicotinic acetylcholine receptor: secondary structure implications.
1994,
Pubmed
Brusés,
Membrane lipid rafts are necessary for the maintenance of the (alpha)7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons.
2001,
Pubmed
Carman,
Regulation of G protein-coupled receptor kinases by caveolin.
1999,
Pubmed
Carozzi,
Inhibition of lipid raft-dependent signaling by a dystrophy-associated mutant of caveolin-3.
2002,
Pubmed
Christian,
Use of cyclodextrins for manipulating cellular cholesterol content.
1997,
Pubmed
Cockcroft,
Ligand-gated ion channels. Homology and diversity.
1990,
Pubmed
Corringer,
Nicotinic receptors at the amino acid level.
2000,
Pubmed
Couet,
Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins.
1997,
Pubmed
Devillers-Thiéry,
Functional architecture of the nicotinic acetylcholine receptor: a prototype of ligand-gated ion channels.
1993,
Pubmed
Engel,
The spectrum of congenital myasthenic syndromes.
2002,
Pubmed
Gasset,
Influence of cholesterol on gramicidin-induced HII phase formation in phosphatidylcholine model membranes.
1988,
Pubmed
Guzmán,
Tryptophan scanning mutagenesis in the alphaM3 transmembrane domain of the Torpedo californica acetylcholine receptor: functional and structural implications.
2003,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Hnasko,
The biology of caveolae: lessons from caveolin knockout mice and implications for human disease.
2003,
Pubmed
Ikonen,
Caveolins and cellular cholesterol balance.
2000,
Pubmed
Ikonen,
Caveolins and membrane cholesterol.
2004,
Pubmed
Jacobson,
Lipid rafts: at a crossroad between cell biology and physics.
2007,
Pubmed
Karlin,
Emerging structure of the nicotinic acetylcholine receptors.
2002,
Pubmed
Lasalde,
Tryptophan substitutions at the lipid-exposed transmembrane segment M4 of Torpedo californica acetylcholine receptor govern channel gating.
1996,
Pubmed
,
Xenbase
Le Novère,
The diversity of subunit composition in nAChRs: evolutionary origins, physiologic and pharmacologic consequences.
2002,
Pubmed
Lee,
Mutations in the M4 domain of Torpedo californica acetylcholine receptor dramatically alter ion channel function.
1994,
Pubmed
,
Xenbase
Malínská,
Visualization of protein compartmentation within the plasma membrane of living yeast cells.
2003,
Pubmed
Marchand,
Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts.
2002,
Pubmed
Margiotta,
The properties and regulation of functional acetylcholine receptors on chick ciliary ganglion neurons.
1987,
Pubmed
McNerney,
Expression and channel properties of alpha-bungarotoxin-sensitive acetylcholine receptors on chick ciliary and choroid neurons.
2000,
Pubmed
Mishina,
Expression of functional acetylcholine receptor from cloned cDNAs.
,
Pubmed
,
Xenbase
Miyazawa,
Structure and gating mechanism of the acetylcholine receptor pore.
2003,
Pubmed
Murata,
VIP21/caveolin is a cholesterol-binding protein.
1995,
Pubmed
Niu,
Manipulation of cholesterol levels in rod disk membranes by methyl-beta-cyclodextrin: effects on receptor activation.
2002,
Pubmed
Ohlsson,
Synthesis and insertion, both in vivo and in vitro, of rat-liver cytochrome P-450 and epoxide hydratase into Xenopus laevis membranes.
1981,
Pubmed
,
Xenbase
Ohtani,
Differential effects of alpha-, beta- and gamma-cyclodextrins on human erythrocytes.
1989,
Pubmed
Okamoto,
Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane.
1998,
Pubmed
Oshikawa,
Nicotinic acetylcholine receptor alpha 7 regulates cAMP signal within lipid rafts.
2003,
Pubmed
Otero-Cruz,
Tryptophan-scanning mutagenesis in the alphaM3 transmembrane domain of the muscle-type acetylcholine receptor. A spring model revealed.
2007,
Pubmed
,
Xenbase
Pike,
Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function.
2006,
Pubmed
Razani,
Caveolae: from cell biology to animal physiology.
2002,
Pubmed
Sadler,
Low-density caveolae-like membrane from Xenopus laevis oocytes is enriched in Ras.
,
Pubmed
,
Xenbase
Santiago,
Tryptophan scanning mutagenesis in the TM3 domain of the Torpedo californica acetylcholine receptor beta subunit reveals an alpha-helical structure.
2004,
Pubmed
,
Xenbase
Santiago,
Probing the effects of membrane cholesterol in the Torpedo californica acetylcholine receptor and the novel lipid-exposed mutation alpha C418W in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Shen,
Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdown.
2006,
Pubmed
Silva,
Identification of caveolae and caveolin in C6 glioma cells.
1999,
Pubmed
Silva,
Caveolin isoform expression during differentiation of C6 glioma cells.
2005,
Pubmed
Tamamizu,
Functional effects of periodic tryptophan substitutions in the alpha M4 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor.
2000,
Pubmed
,
Xenbase
Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed
Unwin,
Nicotinic acetylcholine receptor at 9 A resolution.
1993,
Pubmed
Williams,
The caveolin proteins.
2004,
Pubmed
,
Xenbase
Zhu,
Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering.
2006,
Pubmed