Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking.

Nature cell biology | Jul 1, 2008

Autophagic and endocytic pathways are tightly regulated membrane rearrangement processes that are crucial for homeostasis, development and disease. Autophagic cargo is delivered from autophagosomes to lysosomes for degradation through a complex process that topologically resembles endosomal maturation. Here, we report that a Beclin1-binding autophagic tumour suppressor, UVRAG, interacts with the class C Vps complex, a key component of the endosomal fusion machinery. This interaction stimulates Rab7 GTPase activity and autophagosome fusion with late endosomes/lysosomes, thereby enhancing delivery and degradation of autophagic cargo. Furthermore, the UVRAG-class-C-Vps complex accelerates endosome-endosome fusion, resulting in rapid degradation of endocytic cargo. Remarkably, autophagosome/endosome maturation mediated by the UVRAG-class-C-Vps complex is genetically separable from UVRAG-Beclin1-mediated autophagosome formation. This result indicates that UVRAG functions as a multivalent trafficking effector that regulates not only two important steps of autophagy - autophagosome formation and maturation - but also endosomal fusion, which concomitantly promotes transport of autophagic and endocytic cargo to the degradative compartments.

Pubmed ID: 18552835 RIS Download

Mesh terms: Animals | Apoptosis Regulatory Proteins | Autophagy | Beclin-1 | Cell Line | Endocytosis | Endosomes | Humans | Lysosomes | Membrane Fusion | Membrane Proteins | Mice | Multiprotein Complexes | Phagosomes | Protein Transport | Recombinant Fusion Proteins | Tumor Suppressor Proteins | Vesicular Transport Proteins | rab GTP-Binding Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: R01 HL110609
  • Agency: NIAID NIH HHS, Id: AI 42999
  • Agency: NIAID NIH HHS, Id: R01 AI042999
  • Agency: NCRR NIH HHS, Id: RR00168
  • Agency: NCI NIH HHS, Id: CA82057
  • Agency: NCI NIH HHS, Id: CA91819
  • Agency: NCI NIH HHS, Id: R01 CA082057
  • Agency: NCRR NIH HHS, Id: P51 RR000168
  • Agency: NCRR NIH HHS, Id: K26 RR000168
  • Agency: NCI NIH HHS, Id: CA31363
  • Agency: NIAID NIH HHS, Id: R01 AI069345
  • Agency: NIAID NIH HHS, Id: R01 AI073099-02
  • Agency: NCI NIH HHS, Id: R01 CA091819
  • Agency: NCI NIH HHS, Id: CA106156
  • Agency: NCI NIH HHS, Id: R01 CA106156
  • Agency: NIAID NIH HHS, Id: R01 AI073099
  • Agency: NCI NIH HHS, Id: R01 CA031363
  • Agency: NIAID NIH HHS, Id: AI069345

BioGRID (Data, Interactions)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.