Amplification of CRAC current by STIM1 and CRACM1 (Orai1).
Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium (CRAC) modulator CRACM1 (also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current (I(CRAC)). However, individual overexpression of either protein fails to significantly amplify I(CRAC). Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I(CRAC), suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.
Peinelt
Christine
C
Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI 96813, USA.
Vig
Monika
M
Koomoa
Dana L
DL
Beck
Andreas
A
Nadler
Monica J S
MJ
Koblan-Huberson
Murielle
M
Lis
Annette
A
Fleig
Andrea
A
Penner
Reinhold
R
Kinet
Jean-Pierre
JP
D002118:Calcium / Q000172:deficiency / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D002614:Chelating Agents; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium