Open AccessLipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion
Author(s) -
Joshua A. Lees,
Mirko Messa,
Elizabeth Wen Sun,
Heather Wheeler,
Federico Torta,
Markus R. Wenk,
Pietro De Camilli,
Karin M Reinisch
Publication year - 2017
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aah6171
Subject(s) - endoplasmic reticulum , pulsatile flow , insulin , secretion , cytosol , medicine , endocrinology , chemistry , microbiology and biotechnology , biology , biochemistry , enzyme
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)P 2 ] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P 2 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.