During phospholipase C-β (PLC-β) signalling in Drosophila photoreceptors, the phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS). Depletion of RDGB or its mis-localization away from the ER-PM MCS results in multiple defects in photoreceptor function. Previously, the interaction between the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be essential for accurate localization to ER-PM MCS. Here, we report that the FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this also requires the function of the C-terminal domains, DDHD and LNS2. Mutations in each of these domains results in mis-localization of RDGB leading to loss of function. While the LNS2 domain is necessary, it is not sufficient for the correct localization of RDGB, which also requires the C-terminal DDHD domain. The function of the DDHD domain is mediated through an intramolecular interaction with the LNS2 domain. Thus, interactions between the additional domains in a multi-domain PITP together lead to accurate localization at the MCS and signalling function.

中文翻译：

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域间相互作用调节脂质转移蛋白在ER-PM接触部位的定位

在果蝇感光细胞中的磷脂酶C-β（PLC-β）信号转导期间，内质网（ER）-质膜（PM）接触位点（MCS）的脂质转移需要磷脂酰肌醇转移蛋白（PITP）RDGB。RDGB的耗竭或其远离ER-PM MCS的错误定位会导致感光器功能出现多个缺陷。以前，已显示RDGB的FFAT基序与完整的ER蛋白dVAP-A之间的相互作用对于准确定位到ER-PM MCS是必不可少的。在这里，我们报告仅FFAT / dVAP-A相互作用不足以准确定位RDGB；这也需要C端域DDHD和LNS2的功能。这些结构域中的每一个突变都会导致RDGB定位错误，从而导致功能丧失。虽然LNS2域是必需的，对于RDGB的正确定位是不够的，这也需要C端DDHD域。DDHD结构域的功能是通过与LNS2结构域的分子内相互作用来介导的。因此，多域PITP中其他域之间的交互共同导致MCS和信令功能的准确定位。