Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking (Nat Cell Biol, 2008, 10:776-787)

報告日期: 2008/12/02
報告時間: 16:00/16:50
報告學生: 吳珊瑩
講評老師: 徐麗君
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971202-2.pdf

Beclin1-binding UVRAG targets the class C Vps complex

to coordinate autophagosome maturation

and endocytic trafficking

Nat Cell Biol, 2008, 10:776-787

 

Speaker : 吳珊瑩

Commentator : 徐麗君 老師 

Time :  2008.12.02 ( PM: 4:00~4:50)

Place :  Room 602

 

Abstract

Autophagy is an adaptive response to nutrient starvation. During autophagy, part of the cytoplasm or entire organelles is sequestered into the double-membrane vesicles, called autophagosomes {1}. Autophagosome formation depend on the presence of PI(3)K Class III, which activity is stimulated by Beclin1 binding. Tumour suppressor UVRAG interacts with the Beclin1–PI(3)KC3 complex, promotes PI(3)K activity, and activates autophagosome formation {2}. This paper indicate that UVRAG, interacts with the class C Vps complex, is a key component of the endosomal fusion machinery. Before autophagosomes deliver their content to the lysosome, they undergo a maturation process; they fuse with early and late endosomes, before finally fusing with lysosomes {3}. The interaction between UVRAG and the class C Vps complex can stimulate Rab7 GTPase activity and fusion of autophagosome with late endosomes/lysosomes, thereby enhancing both autophagic and endocytic protein degradation. The dual role of UVRAG in autophagosome biogenesis and maturation places it at the center of the autophagy regulatory network and implies that it is also a key player in endosome biogenesis.

 

References :

1.   Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463–477 (2004).

2.   Liang, C. et al. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nature Cell Biol. 8, 688–699 (2006).

3.   Lucocq, J. & Walker, D. Evidence for fusion between multilamellar endosomes and autophagosomes in HeLa cells. Eur. J. Cell Biol. 72, 307–313 (1997).