scholarly journals Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion

Science ◽  
2017 ◽  
Vol 355 (6326) ◽  
pp. eaah6171 ◽  
Author(s):  
Joshua A. Lees ◽  
Mirko Messa ◽  
Elizabeth Wen Sun ◽  
Heather Wheeler ◽  
Federico Torta ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Secretion ◽  
Lipid Transport ◽  
Membrane Contacts ◽  
Pulsatile Insulin Secretion

scholarly journals Role of phosphodiesterases in the shaping of sub-plasma-membrane cAMP oscillations and pulsatile insulin secretion

2012 ◽  
Vol 125 (21) ◽  
pp. 5084-5095 ◽  
Author(s):  
G. Tian ◽  
J. Sagetorp ◽  
Y. Xu ◽  
H. Shuai ◽  
E. Degerman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Secretion ◽  
Pulsatile Insulin Secretion

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

2019 ◽  
Vol 116 (12) ◽  
pp. 5775-5784 ◽  
Author(s):  
Elizabeth Wen Sun ◽  
Andrés Guillén-Samander ◽  
Xin Bian ◽  
Yumei Wu ◽  
Yiying Cai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neuronal Excitability ◽  
Feedback Mechanism ◽  
Lipid Transport ◽  
Delayed Rectifier ◽  
Lower Sensitivity ◽  
Lipid Exchange ◽  
Membrane Contacts ◽  
Lipid Transporter ◽  
The Brain

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+elevations. ER–PM contacts in neurons are also sites where Kv2 (the major delayed rectifier K+channels in brain) and other PM and ER ion channels are concentrated, raising the possibility of a regulatory feedback mechanism between neuronal excitability and lipid exchange between the ER and the PM.

Pulsatile insulin secretion from isolated human pancreatic islets

Diabetes ◽  
1994 ◽  
Vol 43 (6) ◽  
pp. 827-830 ◽  
Author(s):  
P. Marchetti ◽  
D. W. Scharp ◽  
M. Mclear ◽  
R. Gingerich ◽  
E. Finke ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Human Pancreatic Islets ◽  
Pulsatile Insulin Secretion

scholarly journals The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis

2021 ◽  
Author(s):  
Beichen Xie ◽  
Styliani Panagiotou ◽  
Jing Cen ◽  
Patrick Gilon ◽  
Peter Bergsten ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Insulin Secretion ◽  
Lipid Transfer Protein ◽  
Underlying Mechanism ◽  
Lipid Transfer ◽  
Β Cells ◽  
Transfer Protein ◽  
Lipid Exchange ◽  
Membrane Tethering

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 β-cells, both lipid- and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 dynamically localize to ER-PM contact sites and provide phosphatidylinositol, a precursor of PI(4)P and PI(4,5)P2, to the plasma membrane. β-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 only weakly interact with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Release of TMEM24 into the bulk ER membrane also enables direct interactions with mitochondria, and we report that loss of TMEM24 results in excessive accumulation of Ca2+ in both the ER and mitochondria and in impaired mitochondria function.

Sign in / Sign up

Export Citation Format

Share Document