title: Boundary lipids in the nicotinic acetylcholine receptor microenvironment.
abstract: The structural and functional properties of the nicotinic acetylcholine receptor (AChR), the archetype molecule in the superfamily of Cys-looped ligand-gated ion channels, are strongly dependent on the lipids in the vicinal microenvironment. The influence on receptor properties is mainly exerted by the AChR-vicinal ("shell" or "annular") lipids, which occur in the liquid-ordered phase as opposed to the more disordered and "fluid" bulk membrane lipids. Fluorescence studies from our laboratory have identified discrete sites for fatty acids, phospholipids, and cholesterol on the AChR protein, and electron-spin resonance spectroscopy has enabled the establishment of the stoichiometry and selectivity of the shell lipid for the AChR and the disclosure of lipid sites in the AChR transmembrane region. 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. I surmise that the outermost ring of M4 helices constitutes the boundary interface, most suitable to convey the signals from the lipid microenvironment to the rest of the transmembrane region, and to the channel inner ring in particular.
authors.affiliation: UNESCO Chair of Biophys. & Mol. Neurobiol. and Institute of Biochemistry, Universidad Nacional del Sur-CONICET, C.C. 857, B8000FWB, Bahía, Blanca, Argentina. rtfjb1@criba.edu.ar
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Barrantes
authors.forename: V
authors.initials: V
authors.lastname: Bermudez
authors.forename: M V
authors.initials: MV
authors.lastname: Borroni
authors.forename: S S
authors.initials: SS
authors.lastname: Antollini
authors.forename: M F
authors.initials: MF
authors.lastname: Pediconi
authors.forename: J C
authors.initials: JC
authors.lastname: Baier
authors.forename: I
authors.initials: I
authors.lastname: Bonini
authors.forename: C
authors.initials: C
authors.lastname: Gallegos
authors.forename: A M
authors.initials: AM
authors.lastname: Roccamo
authors.forename: A S
authors.initials: AS
authors.lastname: Valles
authors.forename: V
authors.initials: V
authors.lastname: Ayala
authors.forename: C
authors.initials: C
authors.lastname: Kamerbeek
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000737:chemistry / Q000502:physiology; D005227:Fatty Acids / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000737:chemistry* / Q000502:physiology*; D010743:Phospholipids / Q000737:chemistry / Q000502:physiology; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D013570:Synaptic Membranes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D008563:Membrane Lipids; D010743:Phospholipids; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D002784:Cholesterol
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