Calcium signals mediated by STIM and Orai proteins—A new paradigm in inter-organelle communication

• Published in: Biochimica et biophysica acta 2006-11, Vol.1763 (11), p.1161-1168
• Main Authors: Soboloff, Jonathan, Spassova, Maria A., Dziadek, Marie A., Gill, Donald L.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Calcium; Calcium - metabolism; Calcium Channels - physiology; Calcium Signaling; Calcium signals; Humans; Membrane Proteins - analysis; Membrane Proteins - genetics; Membrane Proteins - physiology; Molecular Sequence Data; Orai; Organelles - chemistry; Organelles - physiology; Protein Structure, Tertiary; STIM; Store-operated channels
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2006.09.023

In all cells Ca 2+ signals are key to controlling a spectrum of cellular responses. Ca 2+ signals activated by phospholipase C-coupled receptors have two components—rapid Ca 2+ release from ER stores followed by slower Ca 2+ entry from outside the cell. The coupling process between ER and PM to mediate this “store-operated” Ca 2+ 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 Ca 2+ binding EF-hand functions as the sensor of ER luminal Ca 2+ and through redistribution in the ER transduces information directly to the PM. Orai1, a tetra-spanning PM protein, functions as the highly Ca 2+ selective channel in the PM that is gated through interactions with the store-activated ER Ca 2+ 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.