Walther Tobias C, Brickner Jason H, Aguilar Pablo S, Bernales Sebastián, Pantoja Carlos, Walter Peter
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California at San Francisco, 600-16th Street, San Francisco, California 94143-2200, USA.
Nature. 2006 Feb 23;439(7079):998-1003. doi: 10.1038/nature04472.
Endocytosis functions to recycle plasma membrane components, to regulate cell-surface expression of signalling receptors and to internalize nutrients in all eukaryotic cells. Internalization of proteins, lipids and other cargo can occur by one of several pathways that have different, but often overlapping, molecular requirements. To mediate endocytosis, effectors assemble transiently underneath the plasma membrane, carry out the mechanics of membrane deformation, cargo selection and vesicle internalization, and then disassemble. The mechanism by which endocytosis initiates at particular locations on the plasma membrane has remained unknown. Sites of endocytosis might be formed randomly, induced by stochastic protein and/or lipid clustering. Alternatively, endocytosis might initiate at specific locations. Here we describe large immobile protein assemblies at the plasma membrane in the yeast Saccharomyces cerevisiae that mark endocytic sites. These structures, termed eisosomes (from the Greek 'eis', meaning into or portal, and 'soma', meaning body), are composed primarily of two cytoplasmic proteins, Pil1 and Lsp1. A plasma membrane protein, Sur7, localizes to eisosomes. These structures colocalize with sites of protein and lipid endocytosis, and their components genetically interact with known endocytic effectors. Loss of Pil1 leads to clustering of eisosome remnants and redirects endocytosis and endocytic effector proteins to these clusters.
内吞作用在所有真核细胞中发挥着回收质膜成分、调节信号受体的细胞表面表达以及内化营养物质的作用。蛋白质、脂质和其他货物的内化可通过几种途径之一发生，这些途径具有不同但通常重叠的分子需求。为了介导内吞作用，效应器在质膜下方短暂组装，执行膜变形、货物选择和囊泡内化的机制，然后解体。内吞作用在质膜特定位置启动的机制仍然未知。内吞位点可能是随机形成的，由随机的蛋白质和/或脂质聚集诱导。或者，内吞作用可能在特定位置启动。在这里，我们描述了酿酒酵母质膜上标记内吞位点的大型固定蛋白组装体。这些结构称为eisosomes（源自希腊语“eis”，意为进入或门户，以及“soma”，意为身体），主要由两种细胞质蛋白Pil1和Lsp1组成。一种质膜蛋白Sur7定位于eisosomes。这些结构与蛋白质和脂质内吞作用的位点共定位，并且它们的成分与已知的内吞效应器发生遗传相互作用。Pil1的缺失导致eisosome残余物的聚集，并将内吞作用和内吞效应蛋白重定向到这些聚集物。
