Ca2+ signaling and STIM1.
An increase in the intracellular calcium ion concentration ([Ca(2+)]) impacts a diverse range of cell functions, including adhesion, motility, gene expression and proliferation. Elevation of intracellular calcium ion (Ca(2+)) regulates various cellular events after the stimulation of cells. Initial increase in Ca(2+) comes from the endoplasmic reticulum (ER), intracellular storage space. However, the continuous influx of extracellular Ca(2+) is required to maintain the increased level of Ca(2+) inside cells. Store-operated Ca(2+) entry (SOCE) manages this process, and STIM1, a newly discovered molecule, has a unique and essential role in SOCE. STIM1 can sense the exhaustion of Ca(2+) in the ER, and activate the SOC channel in the plasma membrane, leading to the continuous influx of extracellular Ca(2+). STIM1 senses the status of the intracellular Ca(2+) stores via a luminal N-terminal Ca(2+)-binding EF-hand domain. Dissociation of Ca(2+) from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca(2+) channels/entry (calcium-release-activated calcium channels/entry). In this review, we summarize the mechanism by which STIM1 regulates SOCE, and also its role in the control of mast cell functions and allergic responses.
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Japan. kurosaki@rcai.riken.jp
Tomohiro
T
Kurosaki
Yoshihiro
Y
Baba
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002413:Cations, Divalent; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
D015220:Calcium Channels; D002413:Cations, Divalent; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium