STIM/Orai signalling complexes in vascular smooth muscle.
Stromal interaction molecules (STIM1 and STIM2) are single pass transmembrane proteins located mainly in the endoplasmic reticulum (ER). STIM proteins contain an EF-hand in their N-termini that faces the lumen side of the ER allowing them to act as ER calcium (Ca(2+)) sensors. STIM1 has been recognized as central to the activation of the highly Ca(2+) selective store-operated Ca(2+) (SOC) entry current mediated by the Ca(2+) release-activated Ca(2+) (CRAC) channel; CRAC channels are formed by tetramers of the plasma membrane (PM) protein Orai1. Physiologically, the production of inositol 1,4,5-trisphosphate (IP(3)) upon stimulation of phospholipase C-coupled receptors and the subsequent emptying of IP(3)-sensitive ER Ca(2+) stores are sensed by STIM1 molecules which aggregate and move closer to the PM to interact physically with Orai1 channels and activate Ca(2+) entry. Orai1 has two homologous proteins encoded by separate genes, Orai2 and Orai3. Other modes of receptor-regulated Ca(2+) entry into cells are store-independent; for example, arachidonic acid activates a highly Ca(2+) selective store-independent channel formed by heteropentamers of Orai1 and Orai3 and regulated by the PM pool of STIM1. Here, I will discuss results pertaining to the roles of STIM and Orai proteins in smooth muscle Ca(2+) entry pathways and their role in vascular remodelling.
The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. trebakm@mail.amc.edu
Mohamed
M
Trebak
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000502:physiology; D058426:Neointima / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
D015220:Calcium Channels; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes