Inter‐organelle communication between closely apposed membranes is proposed at membrane contact sites (MCS). However, the regulation of MCS structure and their functional relevance in vivo remain debated. The extended synaptotagmins (Esyt) are evolutionarily conserved proteins proposed to function at MCS. However, loss of all three Esyts in yeast or mammals shows minimal phenotypes questioning the functional importance of Esyt. We report that in Drosophila photoreceptors, MCS number is regulated by PLCβ activity. Photoreceptors of a null allele of Drosophila extended synaptotagmin (dEsyt) show loss of ER‐PM MCS. Loss of dEsyt results in mislocalization of RDGB, an MCS localized lipid transfer protein, required for photoreceptor structure and function, ultimately leading to retinal degeneration. dEsyt depletion enhanced the retinal degeneration, reduced light responses and slower rates of plasma membrane PIP₂ resynthesis seen in rdgB mutants. Thus, dEsyt function and PLCβ signaling regulate ER‐PM MCS structure and lipid transfer in Drosophila photoreceptors.

中文翻译：

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扩展的突触结合蛋白在体内调节膜接触位点结构和脂质转移功能。

在膜接触位点（MCS）提出了紧密贴合的膜之间的细胞器间通信。然而，MCS 结构的调节及其在体内的功能相关性仍然存在争议。扩展的突触结合蛋白 (Esyt) 是进化上保守的蛋白质，建议在 MCS 发挥作用。然而，酵母或哺乳动物中所有三种 Esyt 的缺失显示出质疑 Esyt 功能重要性的最小表型。我们报告说，在果蝇光感受器中，MCS 数量受 PLCβ 活性的调节。果蝇扩展突触结合蛋白(dEsyt)无效等位基因的光感受器显示 ER-PM MCS 丢失。dEsyt 的缺失导致 RDGB（一种 MCS 定位的脂质转移蛋白）的错误定位，这是感光器结构和功能所必需的，最终导致视网膜变性。在rdgB突变体中， dEsyt耗竭增强了视网膜变性，降低了光反应，降低了质膜 PIP _{2再合成的速率。}因此，dEsyt 功能和 PLCβ 信号调节果蝇光感受器中的 ER-PM MCS 结构和脂质转移。