The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis

Xie, BeichenUppsala universitet,Institutionen för medicinsk cellbiologi (author)

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 beta-cells, both lipid and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 (also known as C2CD2L) dynamically localizes to ER-PM contact sites and provides phosphatidylinositol, a precursor of phosphatidylinositol-4-phosphate [PI(4)P] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2], to the PM. beta-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 onlyweakly interacts with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Loss of TMEM24 results in hyper-accumulation of Ca2+ in the ER and in excess Ca2+ entry into mitochondria, with resulting impairment in glucose-stimulated ATP production.

Panagiotou, StylianiUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)stypa892 (author)
Cen, JingUppsala universitet,Institutionen för medicinsk cellbiologi,Institutionen för kvinnors och barns hälsa,Science for Life Laboratory, SciLifeLab(Swepub:uu)jince383 (author)
Gilon, PatrickCatholic Univ Louvain, Inst Expt & Clin Res IREC, Pole Endocrinol Diabet & Nutr EDIN, Ave Hippocrate 55,B1-55-06, B-1200 Brussels, Belgium. (author)
Bergsten, PeterUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab,Pediatrisk inflammations- och metabolismforskning samt barnhälsa(Swepub:uu)peteberg (author)
Idevall Hagren, Olof,1980-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)olide169 (author)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

By the author/editor: Xie, Beichen; Panagiotou, Styl ...; Cen, Jing; Gilon, Patrick; Bergsten, Peter; Idevall Hagren, ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

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