| RRC ID |
72168
|
| Author |
Horia Vais, Min Wang, Karthik Mallilankaraman, Riley Payne, Chris McKennan, Jeffrey T Lock, Lynn A Spruce, Carly Fiest, Matthew Yan-lok Chan, Ian Parker, Steven H Seeholzer, J Kevin Foskett, Don-On Daniel Mak
|
| Title |
ER-luminal [Ca2+] regulation of InsP3 receptor gating mediated by an ER-luminal peripheral Ca2+-binding protein
|
| Journal |
eLife
|
| Abstract |
Modulating cytoplasmic Ca2+ concentration ([Ca2+]i) by endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+-release channels is a universal signaling pathway that regulates numerous cell-physiological processes. Whereas much is known regarding regulation of InsP3R activity by cytoplasmic ligands and processes, its regulation by ER-luminal Ca2+ concentration ([Ca2+]ER) is poorly understood and controversial. We discovered that the InsP3R is regulated by a peripheral membrane-associated ER-luminal protein that strongly inhibits the channel in the presence of high, physiological [Ca2+]ER. The widely-expressed Ca2+-binding protein annexin A1 (ANXA1) is present in the nuclear envelope lumen and, through interaction with a luminal region of the channel, can modify high-[Ca2+]ER inhibition of InsP3R activity. Genetic knockdown of ANXA1 expression enhanced global and local elementary InsP3-mediated Ca2+ signaling events. Thus, [Ca2+]ER is a major regulator of InsP3R channel activity and InsP3R-mediated [Ca2+]i signaling in cells by controlling an interaction of the channel with a peripheral membrane-associated Ca2+-binding protein, likely ANXA1.
|
| Volume |
9
|
| Published |
2020-5-18
|
| DOI |
10.7554/elife.53531
|
| PMID |
32420875
|
| PMC |
PMC7259957
|
| MeSH |
A549 Cells
Animals
Annexin A1 / metabolism*
Calcium / metabolism*
Calcium Signaling / physiology*
Calcium-Binding Proteins / metabolism
Cell Line, Tumor
Cell Physiological Phenomena / physiology
Chickens
Endoplasmic Reticulum / metabolism*
HEK293 Cells
Humans
Inositol 1,4,5-Trisphosphate / metabolism
Inositol 1,4,5-Trisphosphate Receptors / metabolism*
Ion Channel Gating
Mice
Patch-Clamp Techniques
Rats
|
| IF |
7.08
|
| Resource |
| Human and Animal Cells |
DT40(RCB1464)
IP3R^(-) DT40(RCB1467) |
