
@article {131300,
	title = {Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2.},
	journal = {Elife},
	volume = {12},
	year = {2023},
	month = {07/2023},
	abstract = {<p>Loss of endoplasmic reticular (ER) Ca<sup>2+</sup> activates store-operated Ca<sup>2+</sup> entry (SOCE) by causing the ER localized Ca<sup>2+</sup> sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IP<sub>3</sub>R), an ER-localized IP<sub>3</sub>-gated Ca<sup>2+</sup> channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca<sup>2+</sup> is attenuated by loss of IP<sub>3</sub>Rs, and restored by expression of IP<sub>3</sub>Rs even when they cannot release Ca<sup>2+</sup>, but only if the IP<sub>3</sub>Rs can bind IP<sub>3</sub>. Imaging studies demonstrate that IP<sub>3</sub>Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP<sub>3</sub>-binding site, but not a pore. Convergent regulation by IP<sub>3</sub>Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP<sub>3</sub>.</p>
},
	doi = {10.7554/eLife.80447},
	author = {Chakraborty, P. and Deb, B. K. and Arige, V. and Musthafa, T. and Malik, S. and Yule, D. I. and Taylor, C.W. and Hasan, Gaiti}
}
