Identification of a Binding Motif in the S5 Helix That Confers Cholesterol Sensitivity to the TRPV1 Ion Channel
Por:
Picazo-Juárez G., Romero-Suárez S., Nieto-Posadas A.S., Llorente I., Jara-Oseguera A.S., Briggs M., McIntosh T.J., Simon S.A., Ladrón-de-Guevara E., Islas L.D., Rosenbaum T.
Publicada:
15 jul 2011
Resumen:
The TRPV1 ion channel serves as an integrator of noxious stimuli with its activation linked to pain and neurogenic inflammation. Cholesterol, a major component of cell membranes, modifies the function of several types of ion channels. Here, using measurements of capsaicin-activated currents in excised patches from TRPV1-expressing HEK cells, we show that enrichment with cholesterol, but not its diastereoisomer epicholesterol, markedly decreased wild-type rat TRPV1 currents. Substitutions in the S5 helix, rTRPV1-R579D, and rTRPV1-F582Q, decreased this cholesterol response and rTRPV1-L585I was insensitive to cholesterol addition. Two human TRPV1 variants, with different amino acids at position 585, had different responses to cholesterol with hTRPV1-Ile(585) being insensitive to this molecule. However, hTRPV1-I585L was inhibited by cholesterol addition similar to rTRPV1 with the same S5 sequence. In the absence of capsaicin, cholesterol enrichment also inhibited TRPV1 currents induced by
Filiaciones:
Picazo-Juárez G.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Romero-Suárez S.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Nieto-Posadas A.S.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Llorente I.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Jara-Oseguera A.S.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Briggs M.:
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States
McIntosh T.J.:
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States
Simon S.A.:
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
Ladrón-de-Guevara E.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Islas L.D.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Rosenbaum T.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
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