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.
Kurosaki
Tomohiro
T
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Japan. kurosaki@rcai.riken.jp
Baba
Yoshihiro
Y
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