期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 17, 页码 3330-3344出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.173476
关键词
RDGB; Lipid transfer; Phosphoinositide; PITP
类别
资金
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- National Centre for Biological Sciences-TIFR
- Wellcome Trust-DBT India Alliance
- British Heart Foundation
- BBSRC [BB/J005606/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J005606/1] Funding Source: researchfish
- British Heart Foundation [FS/12/49/29729] Funding Source: researchfish
Many membrane receptors activate phospholipase C (PLC) during signalling, triggering changes in the levels of several plasma membrane lipids including phosphatidylinositol (PtdIns), phosphatidic acid (PtdOH) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2]. It is widely believed that exchange of lipids between the plasma membrane and endoplasmic reticulum (ER) is required to restore lipid homeostasis during PLC signalling, yet the mechanism remains unresolved. RDGBa (hereafter RDGB) is a multi-domain protein with a PtdIns transfer protein (PITP) domain (RDGB-PITPd). We find that, in vitro, the RDGB-PITPd binds and transfers both PtdOH and PtdIns. In Drosophila photoreceptors, which experience high rates of PLC activity, RDGB function is essential for phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for normal phototransduction; however, this property is insufficient to explain the in vivo function because another Drosophila PITP (encoded by vib) that also binds PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants, PtdIns(4,5)P-2 resynthesis at the plasma membrane following PLC activation is delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns and PtdOH, key lipid intermediates during G-protein-coupled PtdIns(4,5)P-2 turnover.
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