Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Derler, I; Jardin, I; Stathopulos, PB; Muik, M; Fahrner, M; Zayats, V; Pandey, SK; Poteser, M; Lackner, B; Absolonova, M; Schindl, R; Groschner, K; Ettrich, R; Ikura, M; Romanin, C.
Cholesterol modulates Orai1 channel function.
Sci Signal. 2016; 9(412):ra10-ra10 Doi: 10.1126/scisignal.aad7808 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Groschner Klaus; Poteser Michael; Schindl Rainer
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Abstract:: STIM1 (stromal interaction molecule 1) and Orai proteins are the essential components of Ca(2+) release-activated Ca(2+) (CRAC) channels. We focused on the role of cholesterol in the regulation of STIM1-mediated Orai1 currents. Chemically induced cholesterol depletion enhanced store-operated Ca(2+) entry (SOCE) and Orai1 currents. Furthermore, cholesterol depletion in mucosal-type mast cells augmented endogenous CRAC currents, which were associated with increased degranulation, a process that requires calcium influx. Single point mutations in the Orai1 amino terminus that would be expected to abolish cholesterol binding enhanced SOCE to a similar extent as did cholesterol depletion. The increase in Orai1 activity in cells expressing these cholesterol-binding-deficient mutants occurred without affecting the amount in the plasma membrane or the coupling of STIM1 to Orai1. We detected cholesterol binding to an Orai1 amino-terminal fragment in vitro and to full-length Orai1 in cells. Thus, our data showed that Orai1 senses the amount of cholesterol in the plasma membrane and that the interaction of Orai1 with cholesterol inhibits its activity, thereby limiting SOCE. Copyright © 2016, American Association for the Advancement of Science.
Find related publications in this database (using NLM MeSH Indexing): Biotinylation -; Calcium - metabolism; Calcium Channels - metabolism; Cell Line -; Cell Membrane - metabolism; Cholesterol - metabolism; Cholesterol Oxidase - metabolism; Circular Dichroism -; Electrophysiological Phenomena -; Fluorescence Resonance Energy Transfer -; HEK293 Cells -; Histamine - metabolism; Humans -; Mast Cells - metabolism; Mutation -; ORAI1 Protein -; Peptides - metabolism; Point Mutation -; Protein Structure, Tertiary -; Signal Transduction -; Spectrometry, Fluorescence -