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PMID: 19946209 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Roles of Pichia pastoris Uvrag in vacuolar protein sorting and the phosphatidylinositol 3-kinase complex in phagophore elongation in autophagy pathways.

Autophagy ·Vol. 6 ·No. 1 ·2010-01-00 ·Pages 86-99

Farré JC, Mathewson RD, Manjithaya R, Subramani S

Abstract

Although it has been established that Atg6/Beclin 1, the phosphatidylinositol 3-kinase (PI3K) Vps34, and associated proteins have direct or indirect roles in autophagic pathways in both mammals and yeasts, the elucidation of these roles and the proteins required for them is ongoing. The involvement of the Beclin 1-binding protein, UVRAG, has been a particular source of disagreement. We found that PpAtg6 is required for all autophagic pathways that have been identified in the yeast Pichia pastoris, as well as for the carboxypeptidase Y (PpCPY) vacuolar protein sorting pathway. We localized PpAtg6 to the phagophore assembly site (PAS) and observed its continued presence at that site as the isolation membrane grew from it and matured into a pexophagosome. PpUvrag, however, was required for proper PpCPY sorting, but not for any autophagic pathway. Rather, the defects in all autophagic pathways observed when PpUvrag was overexpressed support its presence in a complex that competes with the PI3K complex required for autophagy.

MeSH Terms
Adaptor Proteins, Vesicular Transport/genetics,metabolism,physiology Amino Acid Sequence Autophagy/genetics,physiology Endosomal Sorting Complexes Required for Transport/metabolism,physiology Fungal Proteins/genetics,metabolism,physiology Gene Expression Regulation, Fungal Models, Biological Molecular Sequence Data Organisms, Genetically Modified Phagosomes/genetics,metabolism Phosphatidylinositol 3-Kinases/metabolism,physiology Pichia/genetics,metabolism,physiology Sequence Homology, Amino Acid Signal Transduction/genetics,physiology Tissue Distribution Tumor Suppressor Proteins/chemistry,metabolism,physiology
Chemicals
Adaptor Proteins, Vesicular Transport Endosomal Sorting Complexes Required for Transport Fungal Proteins Tumor Suppressor Proteins Phosphatidylinositol 3-Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Farré Jean-Claude
Section of Molecular Biology, Division of Biological Sciences, University California, San Diego, CA, USA.
Mathewson Richard D
Manjithaya Ravi
Subramani Suresh
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Article Info
Journal
Autophagy
Abbr.
Autophagy
ISSN
1554-8635
DOI
10.4161/auto.6.1.10535
Published
2010-01-00
Epub
2010-00-06
Pages
86-99
Language
English
Region
United States
NLM ID
101265188
PMCID
PMC2945526
Subset
IM
Grants
NIGMS NIH HHS · R01 GM069373 · United States
NIGMS NIH HHS · R01 GM069373-05 · United States
NIGMS NIH HHS · GM69373 · United States
External Links
PubMed source DOI: 10.4161/auto.6.1.10535 PMC Full Text View journal details
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