Abstract
Background: ADP-ribosylation factors (ARFs) are a family of small GTP-binding proteins that play roles in membrane dynamics and vesicle trafficking. AGEF-1, which is thought to act as a guanine nucleotide exchange factor of class I ARFs, is required for caveolin-1 body formation and receptor-mediated endocytosis in oocytes of Caenorhabditis elegans. This study explores additional roles of AGEF-1 in endocytic transport. Methods: agef-1 expression was knocked down by using RNAi in C. elegans. Markers that allow analysis of endocytic transport in scavenger cells were investigated for studying the effect of AGEF-1 on different steps of membrane transport. Results: Knockdown of AGEF-1 levels results in two apparent trafficking defects in coelomocytes of C. elegans. First, there is a delay in the uptake of solutes from the extracellular medium. Second, there is a dramatic enlargement of the sizes of lysosomes, even though lysosomal acidification is normal and degradation still occurs. Conclusion: Our results suggest that AGEF-1 regulates endosome/lysosome fusion or fission events, in addition to earlier steps in endocytic transport. General significance: AGEF-1 is the first identified GTPase regulator that functions at the lysosome fusion or fission stage of the endocytic pathway. Our study provides insight into lysosome dynamics in C. elegans.
Original language | English (US) |
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Pages (from-to) | 829-840 |
Number of pages | 12 |
Journal | Biochimica et Biophysica Acta - General Subjects |
Volume | 1820 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2012 |
Keywords
- AGEF-1
- ARF-GEF
- ARL-8
- C. elegans
- Endosomes
- Lysosomes
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology