Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum.
Depletion of intracellular calcium (Ca(2+)) stores induces store-operated Ca(2+) (SOC) entry across the plasma membrane (PM). STIM1, a putative Ca(2+) sensor in the endoplasmic reticulum (ER), has been recently shown to be necessary for SOC channel activation. Here we show that STIM1 dynamically moves in tubulovesicular shape on the ER and its subcompartment in resting living cells, whereas, upon Ca(2+) store depletion, it is rapidly redistributed into discrete puncta that are located underneath, but not inserted into the PM. Normal constitutive movement of STIM1 is mediated through the coiled-coil and Ser/Thr-rich C-terminal domains in the cytoplasmic region of STIM1, whereas subsequent inducible puncta formation further requires the sterile alpha motif domain protruding into the ER lumen. Each of these three domains (coiled-coil, Ser/Thr-rich, and sterile alpha motif) was essential for activating SOC channels. Hence, our findings based on structure-function experiments suggest that constitutive dynamic movement of STIM1 in the ER and its subcompartment is obligatory for subsequent depletion-dependent redistribution of STIM1 into puncta underneath the PM and activation of SOC channels.
Baba
Yoshihiro
Y
Laboratory for Lymphocyte Differentiation and Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Hayashi
Kenji
K
Fujii
Yoko
Y
Mizushima
Akiko
A
Watarai
Hiroshi
H
Wakamori
Minoru
M
Numaga
Takuro
T
Mori
Yasuo
Y
Iino
Masamitsu
M
Hikida
Masaki
M
Kurosaki
Tomohiro
T
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D015220:Calcium Channels; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin