Calcium signals mediated by STIM and Orai proteins--a new paradigm in inter-organelle communication.
In all cells Ca2+ signals are key to controlling a spectrum of cellular responses. Ca2+ signals activated by phospholipase C-coupled receptors have two components-rapid Ca2+ release from ER stores followed by slower Ca2+ entry from outside the cell. The coupling process between ER and PM to mediate this "store-operated" Ca2+ entry process has remained a molecular and mechanistic mystery. Through a combination of high throughput screening and molecular physiological approaches, the machinery and mechanism of this process have been elucidated. Two proteins are key to the coupling process. STIM1, a single spanning membrane protein with an unpaired Ca2+ binding EF-hand functions as the sensor of ER luminal Ca2+ and through redistribution in the ER transduces information directly to the PM. Orai1, a tetra-spanning PM protein, functions as the highly Ca2+ selective channel in the PM that is gated through interactions with the store-activated ER Ca2+ sensor. This molecular pas-de-deux between ER and PM components represents not only a crucial signaling pathway, but also a new paradigm in inter-organelle communication.
Soboloff
Jonathan
J
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA.
Spassova
Maria A
MA
Dziadek
Marie A
MA
Gill
Donald L
DL
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D015388:Organelles / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary
D015220:Calcium Channels; D008565:Membrane Proteins; D002118:Calcium