Hyttinen Juha M T, Niittykoski Minna, Salminen Antero, Kaarniranta Kai
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
Biochim Biophys Acta. 2013 Mar;1833(3):503-10. doi: 10.1016/j.bbamcr.2012.11.018. Epub 2012 Dec 5.
Macroautophagy is an important route in cellular maintenance, in the breakdown and reuse of intracellular materials. It is closely related to endocytosis, the means by which the cell can absorb extracellular material, as both macroautophagy and endocytosis have converging steps and common participating molecules. The point where autophagosomes and endosomes fuse with lysosomes to permit for the final degradation of their contents is important. One of the most substantial molecules in the maturation of autophagosomes/endosomes is Rab7, a member of small GTPases. Rab7 designates the maturation of endosomes and also autophagosomes, directing the trafficking of cargos along microtubules, and finally, participating in the fusion step with lysosomes. Rab7 is an effective multifunctional regulator of autophagy and endocytosis. Since many aggregation-based diseases, e.g. age-related macular degeneration of the eye (AMD) and Alzheimer's disease are due of malfunctioning in the autophagic process, the management of Rab7 activity might hold potential as a therapeutic target against these diseases.
巨自噬是细胞维持、细胞内物质分解和再利用的重要途径。它与内吞作用密切相关,内吞作用是细胞吸收细胞外物质的方式,因为巨自噬和内吞作用都有趋同步骤和共同参与的分子。自噬体和内体与溶酶体融合以允许其内容物最终降解的这一点很重要。自噬体/内体成熟过程中最重要的分子之一是Rab7,它是小GTP酶家族的成员。Rab7标记内体以及自噬体的成熟,指导货物沿微管运输,最终参与与溶酶体的融合步骤。Rab7是自噬和内吞作用的有效多功能调节因子。由于许多基于聚集的疾病,如年龄相关性黄斑变性(AMD)和阿尔茨海默病,都是由于自噬过程功能失调所致,调节Rab7的活性可能具有作为针对这些疾病的治疗靶点的潜力。