IP3 receptors and Ca2+ entry

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Taylor, CW 
Thillaiappan, Nagendra Babu  ORCID logo  https://orcid.org/0000-0001-5641-4067
Hasan, Gaiti 
Pragnya, Chakraborty 

Inositol 1,4,5-trisphosphate receptors (IP3R) are the most widely expressed intracellular Ca2+ release channels. Their activation by IP3 and Ca2+ allows Ca2+ to pass rapidly from the ER lumen to the cytosol. The resulting increase in cytosolic [Ca2+] may directly regulate cytosolic effectors or fuel Ca2+ uptake by other organelles, while the decrease in ER luminal [Ca2+] stimulates store-operated Ca2+ entry (SOCE). We are close to understanding the structural basis of both IP3R activation, and the interactions between the ER Ca2+-sensor, STIM, and the plasma membrane Ca2+ channel, Orai, that lead to SOCE. IP3Rs are the usual means through which extracellular stimuli, through ER Ca2+ release, stimulate SOCE. Here, we review evidence that the IP3Rs most likely to respond to IP3 are optimally placed to allow regulation of SOCE. We also consider evidence that IP3Rs may regulate SOCE downstream of their ability to deplete ER Ca2+ stores. Finally, we review evidence that IP3Rs in the plasma membrane can also directly mediate Ca2+ entry in some cells.

Ca(2+) entry, Ca(2+) puff, Ca(2+) signal, Endoplasmic reticulum, IP(3) receptor, Ryanodine receptor, STIM, Store-operated Ca(2+) entry, Animals, Calcium, Calcium Release Activated Calcium Channels, Calcium Signaling, Humans, Inositol 1,4,5-Trisphosphate Receptors, Stromal Interaction Molecules
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Biochimica et Biophysica Acta
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Wellcome Trust (101844/Z/13/Z)
Biotechnology and Biological Sciences Research Council (BB/P005330/1)