STIM and Orai: the long-awaited constituents of store-operated calcium entry.
Rapid changes in cytosolic Ca(2+) concentrations [Ca(2+)](i) are the most commonly used signals in biology to regulate a whole host of cellular functions including contraction, secretion and gene activation. A widely utilized form of Ca(2+) influx is termed store-operated Ca(2+) entry (SOCE) owing to its control by the Ca(2+) content of the endoplasmic reticulum (ER). The underlying molecular mechanism of SOCE has eluded identification until recently when two groups of proteins, the ER Ca(2+) sensors stromal interaction molecule (STIM)1 and STIM2 and the plasma-membrane channels Orai1, Orai2 and Orai3, have been identified. These landmark discoveries have enabled impressive progress in clarifying how these proteins work in concert and what developmental and cellular processes require their participation most. As we begin to better understand the biology of the STIM and Orai proteins, the attention to the pharmacological tools to influence their functions quickly follow suit. Here, we briefly summarize recent developments in this exciting area of Ca(2+) signaling.
Várnai
Péter
P
Department of Physiology, Semmelweis University Faculty of Medicine, H-1088, Puskin u. 9, Budapest, Hungary. peter.varnai@eok.sote.hu
Hunyady
László
L
Balla
Tamas
T
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000502:physiology*; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071741:ORAI2 Protein; C514506:ORAI2 protein, human; C522867:Orai3 protein, human; C103530:STIM1 protein, human; C513279:STIM2 protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D002118:Calcium