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Nir2 Plays a Central Role in ER‐PM Junctions Maintaining Phosphoinositide Signaling Competence
Author(s) -
Kim Yeun ju,
GuzmanHernandez Maria,
Wisniewski Eva,
Balla Tamas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb177
Subject(s) - phosphatidic acid , diacylglycerol kinase , microbiology and biotechnology , phosphatidylinositol , second messenger system , phospholipase d , chemistry , signal transduction , biology , biochemistry , membrane , phospholipid , protein kinase c
During phospholipase C activation, large amounts of phosphoinositide lipids are consumed while generating the second messengers, diacylglycerol (DG) and InsP 3 . The small PtdIns(4,5)P 2 pool is turned over multiple times and it has been evident that the plasma membrane (PM) inositide pools need to be replenished for sustained signaling with newly synthesized phosphatidylinositol (PtdIns) originating from the ER. Conversely, phosphatidic acid (PtdOH) generated via DG in the PM has to return to the ER where it is utilized for PtdIns synthesis. Although PtdIns transfer protein has been postulated to transport PtdIns from the ER to the PM, the protein responsible for PtdOH transport in the other direction has remained elusive. In this study we used a combination of methods all based on intact cells and found that depletion of Nir2, a homolog of the Drosophila RdgB protein, which has previously been identified as a PtdIns transfer protein, causes a defect both in the utilization of PtdOH at the PM and the synthesis of PtdIns in the ER during PLC activation. Conversely, overexpression of Nir2 facilitates PtdOH removal from the PM and its conversion to PtdIns in agonist‐stimulated cells. These data together with the agonist‐induced translocation of Nir2 into ER‐PM contact sites suggest that Nir2 plays a critical role in the recycling of the lipid products of PLC activation and that the agonist‐induced increased turnover of PtdIns described several decades ago is spatially confined to ER‐PM contact zones.