Rab2 promotes autophagic and endocytic lysosomal degradation

Lőrincz, Péter and Tóth, Sarolta and Benkő, Péter and Lakatos, Zsolt and Boda, Attila and Glatz, Gábor and Hegedűs, Krisztina and Takáts, Szabolcs and Juhász, Gábor (2017) Rab2 promotes autophagic and endocytic lysosomal degradation. JOURNAL OF CELL BIOLOGY, 216 (7). pp. 1937-1947. ISSN 0021-9525

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Abstract

Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting. We also demonstrate that RAB2A is required for autophagosome clearance in human breast cancer cells. In conclusion, we identify Rab2 as a key factor for autophagic and endocytic cargo delivery to and degradation in lysosomes.

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