Different endocytic functions of AGEF-1 in C. elegans coelomocytes

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• 作者：Lichun Tang^a ; Hanna Fares^b ; Xingfu Zhao^a ; Wei Du^a ; ^{weidu@mail.hust.edu.cn} ; Bi-Feng Liu^a ; ^{bfliu@mail.hust.edu.cn}
• 关键词：C. elegans ; Lysosomes ; Endosomes ; ARF-GEF ; AGEF-1 ; ARL-8
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：1820
• 期：7
• 页码：829-840
• 全文大小：1898 K

文摘

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.