Maturation of autophagosomes and endosomes: A key role for Rab7

• Published in: Biochimica et biophysica acta 2013-03, Vol.1833 (3), p.503-510
• Main Authors: Hyttinen, Juha M.T., Niittykoski, Minna, Salminen, Antero, Kaarniranta, Kai
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Cell Physiological Phenomena; Endocytosis; Endosomes - metabolism; Humans; Macular Degeneration - metabolism; Maturation; Phagosomes - metabolism; rab GTP-Binding Proteins - metabolism; Rab7; Trafficking
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2012.11.018

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. ► Autophagy and endosomal degradation processes do converge and also contain common molecules ► Rab7 protein acts in a critical point of maturation process of both autophagosomes and endosomes ► Rab7 takes part in the transportation of autophagosomes and endosomes towards lysosomal degradation ► The action of Rab7 in autophagy and endocytosis is highly regulated ► The control of Rab7 may provide a means to control diseases in which autophagy or endocytosis is disturbed.