Feedback regulation of receptor-induced ca2+ signaling mediated by e-syt1 and nir2 at endoplasmic reticulum-plasma membrane junctions
Journal
Cell Reports
Journal Volume
5
Journal Issue
3
Pages
82-97
Date Issued
2013
Author(s)
Chang, C.L.
Hsieh, T.S.
Rothberg, K.G.
Azizoglu, D.D.
Volk, E.
Liao, J.C.
Liou, J.
Chang, C.L.
Hsieh, T.S.
Rothberg, K.G.
Azizoglu, D.D.
Volk, E.
Liao, J.C.
Liou, J.
Abstract
Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are highly conserved subcellular structures. Despite their importance in Ca(2+) signaling and lipid trafficking, the molecular mechanisms underlying the regulation and functions of ER-PM junctions remain unclear. By developing a genetically encoded marker that selectively monitors ER-PM junctions, we found that the connection between ER and PM was dynamically regulated by Ca(2+) signaling. Elevation of cytosolic Ca(2+) triggered translocation of E-Syt1 to ER-PM junctions to enhance ER-to-PM connection. This subsequently facilitated the recruitment of Nir2, a phosphatidylinositol transfer protein (PITP), to ER-PM junctions following receptor stimulation. Nir2 promoted the replenishment of PM phosphatidylinositol 4,5-bisphosphate (PIP2) after receptor-induced hydrolysis via its PITP activity. Disruption of the enhanced ER-to-PM connection resulted in reduced PM PIP2 replenishment and defective Ca(2+) signaling. Altogether, our results suggest a feedback mechanism that replenishes PM PIP2 during receptor-induced Ca(2+) signaling via the Ca(2+) effector E-Syt1 and the PITP Nir2 at ER-PM junctions.
Publisher
Scopus
Type
journal article