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

doi:10.1016/j.celrep.2013.09.038

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 journal › Article › peer-review

212 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	813-825
Number of pages	13
Journal	Cell Reports
Volume	5
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2013.09.038
State	Published - 2013

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2013.09.038

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@article{6d8b4d224ad14c28bd842d3a063be396,

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

abstract = "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",

author = "Chang, {Chi Lun} and Hsieh, {Ting Sung} and Yang, {T. Tony} and Rothberg, {Karen G.} and Azizoglu, {D. Berfin} and Elzibeth Volk and Liao, {Jung Chi} and Jen Liou",

note = "Funding Information: We are grateful to Dr. Katherine Luby-Phelps at the UT Southwestern Live-Cell Imaging Facility for assistance with electron microscopy and advice, Dr. Elliott Ross for providing histamine H1 receptor plasmid, Dr. Robert Campbell for providing R-GECO1 and GEM-GECO1 plasmids, Dr. Roger Tsien for providing miniSOG plasmids, Dr. Tobias Meyer for providing YFP-Rit tail and GFP-PLCδ-PH plasmids, Dr. Richard Lewis for providing FRB-STIM1 plasmid, Dr. Tamas Balla for providing Orai1-YFP plasmid, Dr. Andrew Tinker for providing Tubby-GFP plasmid, and Linda Patterson for administrative assistance. We thank Dr. James Stull, Dr. Helen Yin, and Dr. Ilya Bezprozvanny for comments on the manuscript. J.L. is a Sowell Family Scholar in Medical Research. This work was supported by Welch Foundation grant I-1789. T.T.Y. and J.-C.L. are supported by NSF grant CMMI-1125760. ",

year = "2013",

doi = "10.1016/j.celrep.2013.09.038",

language = "English (US)",

volume = "5",

pages = "813--825",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

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TY - JOUR

T1 - Feedback regulation of receptor-induced ca2+ signaling mediated by e-syt1 and nir2 at endoplasmic reticulum-plasma membrane junctions

AU - Chang, Chi Lun

AU - Hsieh, Ting Sung

AU - Yang, T. Tony

AU - Rothberg, Karen G.

AU - Azizoglu, D. Berfin

AU - Volk, Elzibeth

AU - Liao, Jung Chi

AU - Liou, Jen

N1 - Funding Information: We are grateful to Dr. Katherine Luby-Phelps at the UT Southwestern Live-Cell Imaging Facility for assistance with electron microscopy and advice, Dr. Elliott Ross for providing histamine H1 receptor plasmid, Dr. Robert Campbell for providing R-GECO1 and GEM-GECO1 plasmids, Dr. Roger Tsien for providing miniSOG plasmids, Dr. Tobias Meyer for providing YFP-Rit tail and GFP-PLCδ-PH plasmids, Dr. Richard Lewis for providing FRB-STIM1 plasmid, Dr. Tamas Balla for providing Orai1-YFP plasmid, Dr. Andrew Tinker for providing Tubby-GFP plasmid, and Linda Patterson for administrative assistance. We thank Dr. James Stull, Dr. Helen Yin, and Dr. Ilya Bezprozvanny for comments on the manuscript. J.L. is a Sowell Family Scholar in Medical Research. This work was supported by Welch Foundation grant I-1789. T.T.Y. and J.-C.L. are supported by NSF grant CMMI-1125760.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

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DO - 10.1016/j.celrep.2013.09.038

M3 - Article

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AN - SCOPUS:84887617011

SN - 2211-1247

VL - 5

SP - 813

EP - 825

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

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

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