Rab2 promotes autophagic and endocytic lysosomal degradation

Lőrincz P, Tóth S, Benkő P, Lakatos Z, Boda A, Glatz G, Zobel M, Bisi S, Hegedűs K, Takáts S, Scita G, Juhász G

J Cell Biol. 2017 Jul. 3: 216 (7): 1937-1947

Speaker: Hsi-Yu, Liu (劉席羽)                                  Time: 15:00~16:00, May 2, 2018

Commentator: Dr. Chang-Shi Chen (陳昌熙老師)           Place: Room 601

Abstract:

 The two main pathways of lysosomal degradation are endocytosis and autophagy. Autophagosomes and endosomes can fuse lysosome and mature into degradative autolysosomes and endolysosomes, respectively. One of the main regulators of intracellular trafficking and vesicle fusion is the Rab small GTPases. The GDP- and GTP-bound forms of Rab proteins have different confirmation. GTP bound to Rab protein leads to the interaction with the effectors. GTP form of Rab controls intracellular membrane traffic, mostly related to vesicular transport, through recruiting specific effector proteins, which tethers the vesicles to the restricted membranes¹. Rab7 is a known regulator of autophagosome–lysosome and endosome–lysosome fusion. The active form GTPase Rab7 binding to its effector, the HOPS( homotypic fusion and protein sorting) complex, together with the adaptor proteins RILP, ORPL1, FYCO1, and PLE KHM1 links the fusion of the endocytic and autophagy pathways with lysosome². Besides Rab7, Rab2 was identified as a direct binding partner of HOPS, and active form Rab2 was found to localize to Rab7-positive vacuoles in cultured Drosophila melanogaster cells. In this paper, the authors found that active form Rab2 binds to HOPS, and promotes autolysosomal fusion. The authors also demonstrated that RAB2A is required for autophagosome clearance in human breast cancer cells. In conclusion, the authors identify Rab2 as a key factor for autophagic and endocytic cargo delivery to the lysosome for degradation.

References:

1          Zhen, Y. & Stenmark, H. Cellular functions of Rab GTPases at a glance. J Cell Sci 128, 3171-3176 (2015).

2          McEwan, D. G. et al. PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Molecular cell 57, 39-54 (2015).