Lipid transport by TMEM24 at ER-plasma membrane contacts regulates pulsatile insulin secretion.
Joshua A LeesMirko MessaElizabeth Wen SunHeather WheelerFederico TortaMarkus R WenkPietro De CamilliKarin M ReinischPublished in: Science (New York, N.Y.) (2017)
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.
Keyphrases
- endoplasmic reticulum
- type diabetes
- glycemic control
- estrogen receptor
- particulate matter
- air pollution
- protein kinase
- induced apoptosis
- fatty acid
- working memory
- heavy metals
- metabolic syndrome
- risk assessment
- polycyclic aromatic hydrocarbons
- molecular dynamics simulations
- skeletal muscle
- oxidative stress
- dna binding
- endoplasmic reticulum stress
- cell death
- small molecule
- amino acid