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. 2025 May 5;224(5):e202407190.
doi: 10.1083/jcb.202407190. Epub 2025 Mar 5.

Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors

Vaisaly R Nath  1   2 , Harini Krishnan  1 , Shirish Mishra  1 , Padinjat Raghu  1
Affiliations

Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors

Vaisaly R Nath et al. J Cell Biol. .

Abstract

Membrane contact sites (MCS) between the plasma membrane (PM) and endoplasmic reticulum (ER) regulate Ca2+ influx. However, the mechanisms by which cells modulate ER-PM MCS density are not understood, and the role of Ca2+, if any, in regulating these is unknown. We report that in Drosophila photoreceptors, MCS density is regulated by the Ca2+ channels, TRP and TRPL. Regulation of MCS density by Ca2+ is mediated by Drosophila extended synaptotagmin (dEsyt), a protein localized to ER-PM MCS and previously shown to regulate MCS density. We find that the Ca2+-binding activity of dEsyt is required for its function in vivo. dEsytCaBM, a Ca2+ non-binding mutant of dEsyt is unable to modulate MCS structure. Further, reconstitution of dEsyt null photoreceptors with dEsytCaBM is unable to rescue ER-PM MCS density and other key phenotypes. Thus, our data supports a role for Ca2+ binding to dEsyt in regulating ER-PM MCS density in photoreceptors thus tuning signal transduction during light-activated Ca2+ influx.

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Conflict of interest statement

Disclosures: The authors declare no competing interests exist.

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