Please use this identifier to cite or link to this item: https://doi.org/10.1126/science.aah6171
Title: Lipid transport by TMEM24 at ER-plasma membrane contacts regulates pulsatile insulin secretion
Authors: Lees, Joshua A
Messa, Mirko
Sun, Elizabeth Wen
Wheeler, Heather
Torta, Federico
Wenk, Markus R 
De Camilli, Pietro
Reinisch, Karin M
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
BINDING PROTEINS
PHOSPHATIDYLSERINE TRANSPORT
CALCIUM OSCILLATIONS
TULIP SUPERFAMILY
SMP DOMAINS
EXCHANGE
PHOSPHOLIPIDS
SITES
PHOSPHORYLATION
IDENTIFICATION
Issue Date:  17
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Citation: Lees, Joshua A, Messa, Mirko, Sun, Elizabeth Wen, Wheeler, Heather, Torta, Federico, Wenk, Markus R, De Camilli, Pietro, Reinisch, Karin M (17). Lipid transport by TMEM24 at ER-plasma membrane contacts regulates pulsatile insulin secretion. SCIENCE 355 (6326). ScholarBank@NUS Repository. https://doi.org/10.1126/science.aah6171
Abstract: Copyright 2016 by the American Association for the Advancement of Science; all rights reserved. Insulin is released by β cells in pulses regulated by calcium and phosphoinositide signaling. Here, we describe how transmembrane protein 24 (TMEM24) helps coordinate these signaling events. We showed that TMEM24 is an endoplasmic reticulum (ER)-anchored membrane protein whose reversible localization to ER-plasma membrane (PM) contacts is governed by phosphorylation and dephosphorylation in response to oscillations in cytosolic calcium. A lipid-binding module in TMEM24 transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P2 hydrolyzed during signaling. In the absence of TMEM24, calcium oscillations are abolished, leading to a defect in triggered insulin release. Our findings implicate direct lipid transport between the ER and the PM in the control of insulin secretion, a process impaired in patients with type II diabetes.
Source Title: SCIENCE
URI: https://scholarbank.nus.edu.sg/handle/10635/173253
ISSN: 00368075
10959203
DOI: 10.1126/science.aah6171
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