期刊
FASEB JOURNAL
卷 35, 期 6, 页码 -出版社
WILEY
DOI: 10.1096/fj.202100487R
关键词
acidocalcisome; endocytosis; HOPS; lysosome; Trypanosoma brucei; Vps41
资金
- HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [AI077538]
In Trypanosoma brucei, down-regulation of Vps41 expression through RNAi leads to significant inhibition of endocytosis, affecting cell growth, while other functions of Vps41 in mammalian and yeast cells remain unaffected. The essentiality of TbVps41 suggests it as a potential drug target.
The bloodstream stage of Trypanosoma brucei, the causative agent of African trypanosomiasis, is characterized by its high rate of endocytosis, which is involved in remodeling of its surface coat. Here we present evidence that RNAi-mediated expression down-regulation of vacuolar protein sorting 41 (Vps41), a component of the homotypic fusion and vacuole protein sorting (HOPS) complex, leads to a strong inhibition of endocytosis, vesicle accumulation, enlargement of the flagellar pocket (big eye phenotype), and dramatic effect on cell growth. Unexpectedly, other functions described for Vps41 in mammalian cells and yeasts, such as delivery of proteins to lysosomes, and lysosome-related organelles (acidocalcisomes) were unaffected, indicating that in trypanosomes post-Golgi trafficking is distinct from that of mammalian cells and yeasts. The essentiality of TbVps41 suggests that it is a potential drug target.
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