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bioRxiv · 10.1101/2022.04.12.488111

Regulation of Store-Operated Ca2+ Entry by IP3 Receptors Independent of Their Ability to Release Ca2+

Chakraborty, P.·Deb, B. K.·Taylor, C. W.·Hasan, G.
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Abstract

Loss of endoplasmic reticular (ER) Ca2+ activates store-operated Ca2+ entry (SOCE) by causing the ER localized Ca2+ 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 (IP3R), an ER-localized IP3-gated Ca2+ channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca2+ is attenuated by loss of IP3Rs, and restored by expression of IP3Rs even when they cannot release Ca2+, but only if the IP3Rs can bind IP3. Imaging studies demonstrate that IP3Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP3-binding site, but not a pore. Convergent regulation by IP3Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP3.

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Chakraborty, P., Deb, B. K., Taylor, C. W., Hasan, G.. 2022-04-13. Regulation of Store-Operated Ca2+ Entry by IP3 Receptors Independent of Their Ability to Release Ca2+. https://doi.org/10.1101/2022.04.12.488111

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