PT  - JOURNAL ARTICLE
AU  - Beichen Xie
AU  - Styliani Panagiotou
AU  - Jing Cen
AU  - Patrick Gilon
AU  - Peter Bergsten
AU  - Olof Idevall-Hagren
TI  - The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca<sup>2+</sup> homeostasis
AID  - 10.1101/2021.06.23.449694
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.23.449694
4099  - http://biorxiv.org/content/early/2021/06/24/2021.06.23.449694.short
4100  - http://biorxiv.org/content/early/2021/06/24/2021.06.23.449694.full
AB  - Endoplasmic reticulum (ER) - plasma membrane (PM) contacts are sites of lipid exchange and Ca2+ transport, and both lipid transport proteins and Ca2+ channels specifically accumulate at these locations. In pancreatic β-cells, both lipid- and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 dynamically localize to ER-PM contact sites and provide phosphatidylinositol, a precursor of PI(4)P and PI(4,5)P2, to the plasma membrane. β-cells lacking TMEM24 exhibit markedly suppressed glucose-induced Ca2+ oscillations and insulin secretion but the underlying mechanism is not known. We now show that TMEM24 only weakly interact with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Release of TMEM24 into the bulk ER membrane also enables direct interactions with mitochondria, and we report that loss of TMEM24 results in excessive accumulation of Ca2+ in both the ER and mitochondria and in impaired mitochondria function.Competing Interest StatementThe authors have declared no competing interest.