Cholesterol modulates the cellular localization of Orail channels and its disposition among membrane domains
Por:
Bohorquez-Hernandez, A., Gratton, Enrico, Pacheco, Jonathan, Asanov, Alexander, Vaca, Luis
Publicada:
1 dic 2017
Resumen:
Store Operated Calcium Entry (SOCE) is one of the most important
mechanisms for calcium mobilization in to the cell. Two main proteins
sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic
reticulum (ER) and Orai1 responsible for calcium influx upon depletion
of ER. There are many studies indicating that SOCE is modulated by the
cholesterol content of the plasma membrane (PM). However, a myriad of
questions remain unanswered concerning the precise molecular mechanism
by which cholesterol modulates SOCE.
In the present study we found that reducing PM cholesterol results in
the internalization of Orai1 channels, which can be prevented by
overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate
upon SOCE activation as revealed by FRET and coimmunoprecipitation
assays. The effects of reducing cholesterol were not limited to an
increased rate of Orai1 internalization, but also, affects the lateral
movement of Orai1, inducing movement in a linear pattern (unobstructed
diffusion) opposite to basal cholesterol conditions were most of Orai1
channels moves in a confined space, as assessed by Fluorescence
Correlation Spectroscopy, Cav1 overexpression inhibited these
alterations maintaining Orai1 into a confined and partially confined
movement.
These results not only highlight the complex effect of cholesterol
regulation on SOCE, but also indicate a direct regulatory effect on
Orai1 localization and compartmentalization by this lipid.
Filiaciones:
Bohorquez-Hernandez, A.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City, DF, Mexico
Gratton, Enrico:
Univ Calif Irvine, Dept Biomed Engn, 3210 Nat Sci 2, Irvine, CA 92697 USA
Pacheco, Jonathan:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City, DF, Mexico
Asanov, Alexander:
TIRF Labs Inc, 106 Grendon Pl, Cary, NC 27519 USA
Vaca, Luis:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City, DF, Mexico
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