title: Physiological function and molecular basis of STIM1-mediated calcium entry in immune cells.
abstract: Calcium signals in immune cells regulate a variety of physiological responses such as cell activation, differentiation, gene transcription, and effector functions. Surface receptor stimulation induces an increase in the concentration of cytosolic calcium ions (Ca2+), which are derived mainly from two sources, intracellular endoplasmic reticulum (ER) Ca2+ stores and the extracellular space. The major cascade for Ca2+ entry in immune cells is through store-operated Ca2+ entry (SOCE) and Ca2+ release-activated Ca2+ (CRAC) channels. Activation of SOCE is triggered by depletion of intracellular ER Ca2+ stores, but the molecular mechanism was a long-standing issue. With the recent molecular identification of the ER Ca2+ sensor [stromal interacting molecule-1 (STIM1)] and a pore-forming subunit of the CRAC channel (Orai1), our understanding of the SOCE activation pathway has increased dramatically. These advances have now made it possible to shed some light on important questions: what is the physiological significance of SOCE, and what is its molecular basis? This review focuses on the recent progress in the field and the exciting opportunities for understanding how SOCE influences diverse immune functions.
authors.affiliation: Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan. babay@rcai.riken.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D002118:Calcium