Retrograde traffic modulates contact site formation at the ER and the Golgi (P20*)

囊泡转运是脂类和蛋白质沿内膜系统分布或最终由细胞分泌的一种有效途径。在分泌途径中，COPI囊泡被确保从高尔基体逆行运输到内质网(ER)。公认的逆行转运功能是脂类和正向转运蛋白机制的循环，以及逃逸的内质网驻留蛋白的找回。在这里，我们提出了一种新的功能，逆行交通沿早期分泌途径的接触蛋白的分布。这一假说预测，内质网和跨高尔基网络(TGN)的接触部位形成的程度分别受COPI依赖的囊泡交通活动的调节。沿着这些思路，我们最近发现了几个接触位点蛋白与COPI相互作用。在这个方案中，我们将他们的COPI识别基序和各自的识别结构域映射到COPI上。我们将测试COPI对它们的识别的监管是否会影响不同联系地点的相对分布或其功能。

Vesicular transport is an efficient means by which lipids and proteins are distributed along the endomembrane system or eventually secreted from cells. Within the secretory pathway, the COPI vesicle coat operates to ensure retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Recognized functions of retrograde transport are the recycling of lipids and forward-transport protein machinery as well as the retrieval of escaped ER-resident proteins. Here, we propose a novel function of retrograde traffic in the distribution of contact-site proteins along the early secretory pathway. This hypothesis predicts that the respective extent of contact site formation at the ER and the trans-Golgi network (TGN) is regulated by the activity of COPI-dependent vesicular traffic. Along those lines, we have recently discovered that several contact site proteins interact with COPI. In this proposal, we will map their COPI recognition motifs and the respective recognition domains on COPI. We will test whether the regulation of their recognition by COPI affects the relative distribution of different contact sites or their functionality.