OSBP-homologous proteins (ORPs, Oshp) are lipid binding/transfer proteins. Several ORP/Oshp localize to membrane contacts between the endoplasmic reticulum (ER) and the plasma membrane, where they mediate lipid transfer or regulate lipid-modifying enzymes. A common way in which they target contacts is by binding to the ER proteins, VAP/Scs2p, while the second membrane is targeted by other interactions with lipids or proteins.We have studied the cross-talk of secretory SNARE proteins and their regulators with ORP/Oshp and VAPA/Scs2p at ER-plasma membrane contact sites in yeast and murine primary neurons. We show that Oshp-Scs2p interactions depend on intact secretory SNARE proteins, especially Sec9p. SNAP-25/Sec9p directly interact with ORP/Osh proteins and their disruption destabilized the ORP/Osh proteins, associated with dysfunction of VAPA/Scs2p. Deleting OSH1-3 in yeast or knocking down ORP2 in primary neurons reduced the oligomerization of VAPA/Scs2p and affected their multiple interactions with SNAREs. These observations reveal a novel cross-talk between the machineries of ER-plasma membrane contact sites and those driving exocytosis.

中文翻译：

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ORP / Osh介导ER-质膜接触部位成分与质膜SNARE之间的串扰。

OSBP同源蛋白（ORP，Oshp）是脂质结合/转移蛋白。几种ORP / Oshp定位于内质网（ER）与质膜之间的膜接触，在其中它们介导脂质转移或调节脂质修饰酶。它们靶向接触的一种常见方式是与ER蛋白VAP / Scs2p结合，而第二层膜则通过与脂质或蛋白的其他相互作用而靶向。我们研究了分泌型SNARE蛋白及其与ORP的调节剂的串扰。 / Oshp和VAPA / Scs2p在酵母和小鼠原代神经元的ER-质膜接触位点。我们表明，Oshp-Scs2p相互作用取决于完整的分泌性SNARE蛋白，尤其是Sec9p。SNAP-25 / Sec9p直接与ORP / Osh蛋白相互作用，并且破坏它们会破坏ORP / Osh蛋白的稳定性，与VAPA / Scs2p功能障碍有关。删除酵母中的OSH1-3或敲除原代神经元中的ORP2可减少VAPA / Scs2p的寡聚并影响其与SNARE的多重相互作用。这些观察结果揭示了ER-质膜接触位点的机械与驱动胞吐作用的机械之间的新型串扰。