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The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis
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- Xie, Beichen (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Panagiotou, Styliani (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Cen, Jing (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Institutionen för kvinnors och barns hälsa,Science for Life Laboratory, SciLifeLab
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- (creator_code:org_t)
- 2021-12-16
- 2022
- English.
- In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 135:5
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Membrane contact sites
- Ca2
- Insulin secretion
- Phosphoinositides
- Mitochondria
Publication and Content Type
- ref (subject category)
- art (subject category)
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