Lipid transporter TMEM24/C2CD2L is a Ca2+ -regulated component of ER-plasma membrane contacts in mammalian neurons

Proceedings of the National Academy of Sciences of the United States of America
Elizabeth Wen SunPietro De Camilli

Abstract

Close appositions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are a general feature of all cells and are abundant in neurons. A function of these appositions is lipid transport between the two adjacent bilayers via tethering proteins that also contain lipid transport modules. However, little is known about the properties and dynamics of these proteins in neurons. Here we focused on TMEM24/C2CD2L, an ER-localized SMP domain containing phospholipid transporter expressed at high levels in the brain, previously shown to be a component of ER-PM contacts in pancreatic β-cells. TMEM24 is enriched in neurons versus glial cells and its levels increase in parallel with neuronal differentiation. It populates ER-PM contacts in resting neurons, but elevations of cytosolic Ca2+ mediated by experimental manipulations or spontaneous activity induce its transient redistribution throughout the entire ER. Dissociation of TMEM24 from the plasma membrane is mediated by phosphorylation of an array of sites in the C-terminal region of the protein. These sites are only partially conserved in C2CD2, the paralogue of TMEM24 primarily expressed in nonneuronal tissues, which correspondingly display a much lower sensitivity to Ca2+ ...Continue Reading

Citations

Jul 20, 2019·Nature Chemical Biology·Xin BianChenxiang Lin
Mar 3, 2020·Frontiers in Neuroscience·Zeynep ÖztürkJuan José Pérez-Moreno
Jan 23, 2021·Nature Communications·Xiongwen CaoSarah A Slavoff
Sep 19, 2020·Current Opinion in Physiology·Tamas BallaJoshua Pemberton
Feb 24, 2020·Current Opinion in Cell Biology·Christopher J Stefan
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Chenlu LiHaijia Yu
Mar 9, 2021·Frontiers in Cell and Developmental Biology·Bailey HewlettThierry Galli
Apr 24, 2021·The Journal of Cell Biology·Andrés Guillén-SamanderPietro De Camilli
May 2, 2021·Current Opinion in Cell Biology·Rossella VendittiMaria Antonietta De Matteis
May 3, 2021·The Journal of Biological Chemistry·Tiantian QianHaijia Yu
Aug 6, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Denisa Jamecna, Bruno Antonny

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