Baba Yoshihiro, Hayashi Kenji, Fujii Yoko, Mizushima Akiko, Watarai Hiroshi, Wakamori Minoru, Numaga Takuro, Mori Yasuo, Iino Masamitsu, Hikida Masaki, Kurosaki Tomohiro
Laboratory for Lymphocyte Differentiation and Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16704-9. doi: 10.1073/pnas.0608358103. Epub 2006 Oct 30.
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.
细胞内钙（Ca(2+)）储备的耗竭会诱导钙库操纵的Ca(2+)（SOC）通过质膜（PM）进入细胞。基质相互作用分子1（STIM1）是内质网（ER）中一种假定的Ca(2+)传感器，最近已证明其对SOC通道激活是必需的。在此我们表明，在静息的活细胞中，STIM1在内质网及其亚区室上以管状小泡的形态动态移动，而在Ca(2+)储备耗竭时，它会迅速重新分布到位于质膜下方但未插入质膜的离散斑点中。STIM1正常的组成型移动是通过STIM1胞质区域中的卷曲螺旋和富含丝氨酸/苏氨酸的C末端结构域介导的，而随后的诱导性斑点形成进一步需要突出到内质网腔中的无活性α基序结构域。这三个结构域（卷曲螺旋、富含丝氨酸/苏氨酸和无活性α基序）中的每一个对于激活SOC通道都是必不可少的。因此，我们基于结构 - 功能实验的发现表明，STIM1在内质网及其亚区室中的组成型动态移动对于随后STIM1依赖于储备耗竭的重新分布到质膜下方的斑点以及SOC通道的激活是必不可少的。
