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PMID: 19158398 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The SM protein Car/Vps33A regulates SNARE-mediated trafficking to lysosomes and lysosome-related organelles.

Molecular biology of the cell ·Vol. 20 ·No. 6 ·2009-03-00 ·Pages 1705-14

Akbar MA, Ray S, Krämer H

Abstract

The SM proteins Vps33A and Vps33B are believed to act in membrane fusions in endosomal pathways, but their specific roles are controversial. In Drosophila, Vps33A is the product of the carnation (car) gene. We generated a null allele of car to test its requirement for trafficking to different organelles. Complete loss of car function is lethal during larval development. Eye-specific loss of Car causes late, light-independent degeneration of photoreceptor cells. Earlier in these cells, two distinct phenotypes were detected. In young adults, autophagosomes amassed indicating that their fusion with lysosomes requires Car. In eye discs, endocytosed receptors and ligands accumulate in Rab7-positive prelysosomal compartments. The requirement of Car for late endosome-to-lysosome fusion in imaginal discs is specific as early endosomes are unaffected. Furthermore, lysosomal delivery is not restored by expression of dVps33B. This specificity reflects the distinct pattern of binding to different Syntaxins in vitro: dVps33B predominantly binds the early endosomal Avl and Car to dSyntaxin16. Consistent with a role in Car-mediated fusion, dSyntaxin16 is not restricted to Golgi membranes but also present on lysosomes.

MeSH Terms
Animals Cell Line DNA-Binding Proteins/genetics,metabolism Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,growth & development,metabolism,ultrastructure Endocytosis Eye Proteins/genetics,metabolism Lysosomes/metabolism Microscopy, Electron Protein Binding Protein Transport SNARE Proteins/genetics,metabolism Syntaxin 16/metabolism
Chemicals
DNA-Binding Proteins Drosophila Proteins Eye Proteins SNARE Proteins Syntaxin 16 car protein, Drosophila syntaxin 16, Drosophila
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Akbar Mohammed A
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Ray Sanchali
Krämer Helmut
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e08-03-0282
Published
2009-03-00
Epub
2009-00-21
Pages
1705-14
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2655250
Subset
IM
Grants
NEI NIH HHS · R01 EY010199 · United States
NEI NIH HHS · EY10199 · United States
External Links
PubMed source DOI: 10.1091/mbc.e08-03-0282 PMC Full Text View journal details
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