Luzio J Paul, Poupon Viviane, Lindsay Margaret R, Mullock Barbara M, Piper Robert C, Pryor Paul R
Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK.
Mol Membr Biol. 2003 Apr-Jun;20(2):141-54. doi: 10.1080/0968768031000089546.
Lysosomes are dynamic organelles receiving membrane traffic input from the biosynthetic, endocytic and autophagic pathways. They may be regarded as storage organelles for acid hydrolases and are capable of fusing with late endosomes to form hybrid organelles where digestion of endocytosed macromolecules occurs. Reformation of lysosomes from the hybrid organelles involves content condensation and probably removal of some membrane proteins by vesicular traffic. Lysosomes can also fuse with the plasma membrane in response to cell surface damage and a rise in cytosolic Ca(2+) concentration. This process is important in plasma membrane repair. The molecular basis of membrane traffic pathways involving lysosomes is increasingly understood, in large part because of the identification of many proteins required for protein traffic to vacuoles in the yeast Saccharomyces cerevisiae. Mammalian orthologues of these proteins have been identified and studied in the processes of vesicular delivery of newly synthesized lysosomal proteins from the trans-Golgi network, fusion of lysosomes with late endosomes and sorting of membrane proteins into lumenal vesicles. Several multi-protein oligomeric complexes required for these processes have been identified. The present review focuses on current understanding of the molecular mechanisms of fusion of lysosomes with both endosomes and the plasma membrane and on the sorting events required for delivery of newly synthesized membrane proteins, endocytosed membrane proteins and other endocytosed macromolecules to lysosomes.
溶酶体是动态细胞器，接收来自生物合成、内吞和自噬途径的膜转运输入。它们可被视为酸性水解酶的储存细胞器，能够与晚期内体融合形成混合细胞器，在其中发生内吞大分子的消化。从混合细胞器中重新形成溶酶体涉及内容物浓缩，并且可能通过囊泡运输去除一些膜蛋白。溶酶体也可响应细胞表面损伤和胞质Ca(2+)浓度升高而与质膜融合。这一过程在质膜修复中很重要。涉及溶酶体的膜转运途径的分子基础越来越为人所知，这在很大程度上是由于鉴定出了酿酒酵母中蛋白质转运至液泡所需的许多蛋白质。这些蛋白质的哺乳动物直系同源物已在从反式高尔基体网络新合成的溶酶体蛋白的囊泡运输、溶酶体与晚期内体的融合以及膜蛋白分选到腔内小泡的过程中得到鉴定和研究。已经鉴定出了这些过程所需的几种多蛋白寡聚复合物。本综述重点关注目前对溶酶体与内体和质膜融合的分子机制的理解，以及将新合成的膜蛋白、内吞膜蛋白和其他内吞大分子递送至溶酶体所需的分选事件。
