Feedback regulation of receptor-induced ca2+ signaling mediated by e-syt1 and nir2 at endoplasmic reticulum-plasma membrane junctions

Chi Lun Chang, Ting Sung Hsieh, T. Tony Yang, Karen G. Rothberg, D. Berfin Azizoglu, Elzibeth Volk, Jung Chi Liao, Jen Liou

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are highly conserved subcellular structures. Despite their importance in Ca2+ 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 Ca2+ signaling. Elevation of cytosolic Ca2+ 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 anddefective Ca2+ signaling. Altogether, our results suggest a feedback mechanism that replenishes PM PIP2 during receptor-induced Ca2+ signaling viathe Ca2+ effector E-Syt1 and the PITP Nir2 at ER-PM junctions

Original languageEnglish (US)
Pages (from-to)813-825
Number of pages13
JournalCell Reports
Issue number3
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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