Feedback Regulation of Receptor-Induced Ca2+ Signaling Mediated by E-Syt1 and Nir2 at Endoplasmic Reticulum-Plasma Membrane Junctions

Autor: Chi-Lun Chang, Ting-Sung Hsieh, T. Tony Yang, Karen G. Rothberg, D. Berfin Azizoglu, Elzibeth Volk, Jung-Chi Liao, Jen Liou
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Cell Reports, Vol 5, Iss 3, Pp 813-825 (2013)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2013.09.038
Popis: 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 and defective Ca2+ signaling. Altogether, our results suggest a feedback mechanism that replenishes PM PIP2 during receptor-induced Ca2+ signaling via the Ca2+ effector E-Syt1 and the PITP Nir2 at ER-PM junctions.
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