OSBP-related protein 4L promotes phospholipase C3 translocation from the nucleus to the plasma membrane in Jurkat T-cells
OSBP-related protein 4L promotes phospholipase C3 translocation from the nucleus to the plasma membrane in Jurkat T-cells
复制标题
OSBP 相关蛋白 4L 促进 Jurkat T 细胞中磷脂酶 C3 从细胞核易位至质膜
DOI：
10.1074/jbc.ra118.005437
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发表时间：
2018-11-09
影响因子：
4.8
通讯作者：
Yan, Daoguang
中科院分区：
文献类型：
--
作者：
Pan, Guoping;Cao, Xiuye;Yan, Daoguang
Phosphoinositide phospholipases C (PLCs) are a family of eukaryotic intracellular enzymes with important roles in signal transduction. In addition to their location at the plasma membrane, PLCs also exist within the cell nucleus where they are stored. We previously demonstrated that OSBP-related protein 4L (ORP4L) anchors cluster of differentiation 3E (CD3E) to the heterotrimeric G protein subunit (G(q/11)) to control PLC3 relocation and activation. However, the underlying mechanism by which ORP4L facilitates PLC3 translocation remains unknown. Here, using confocal immunofluorescence microscopy and coimmunoprecipitation assays, we report that ORP4L stimulates PLC3 translocation from the nucleus to the plasma membrane in Jurkat T-cells in two steps. First, we found that ORP4L is required for the activation of Ras-related nuclear protein (RAN), a GTP-binding nuclear protein that binds to exportin 1 and eventually promotes the nuclear export of PLC3. Second, we also observed that ORP4L interacts with vesicle-associated membrane protein-associated protein A (VAPA) through its two phenylalanines in an acidic tract (FFAT) motif. This complex enabled PLC3 movement to the plasma membrane, indicating that PLC3 translocation occurs in a VAPA-dependent manner. This study reveals detailed mechanistic insight into the role of ORP4L in PLC3 redistribution from storage within the nucleus to the plasma membrane via RAN activation and interaction with VAPA in Jurkat T-cells.
