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.

Rab2 promotes autophagic and endocytic lysosomal degradation / P. Lörincz, S. Tóth, P. Benkö, Z. Lakatos, A. Boda, G. Glatz, M. Zobel, S. Bisi, K. Hegedüs, S. Takáts, G. Scita, G. Juhász. - In: THE JOURNAL OF CELL BIOLOGY. - ISSN 0021-9525. - 216:7(2017 Jul 03), pp. 1937-1947. [10.1083/jcb.201611027]

Rab2 promotes autophagic and endocytic lysosomal degradation

M. Zobel
Investigation
;
S. Bisi
Methodology
;
G. Scita
Writing – Review & Editing
;
2017

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.
Animals; Animals, Genetically Modified; Autophagosomes; Breast Neoplasms; Cell Line, Tumor; Drosophila Proteins; Drosophila melanogaster; Endosomes; Female; Humans; Lysosomes; Membrane Fusion; Proteolysis; RNA Interference; Signal Transduction; Transfection; rab GTP-Binding Proteins; rab2 GTP-Binding Protein; Autophagy; Endocytosis; Cell Biology
Settore MED/04 - Patologia Generale
3-lug-2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/551269
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