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TbVps41 regulates trafficking of endocytic but not biosynthetic cargo to lysosomes of bloodstream forms of Trypanosoma brucei
Author(s) -
Ramakrishnan Srinivasan,
Baptista Rodrigo P.,
Asady Beejan,
Huang Guozhong,
Docampo Roberto
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100487r
Subject(s) - trypanosoma brucei , endocytic cycle , endocytosis , microbiology and biotechnology , vacuole , golgi apparatus , biology , lysosome , organelle , vacuolar protein sorting , endosome , protein targeting , cell , biochemistry , cytoplasm , membrane protein , intracellular , gene , endoplasmic reticulum , enzyme , membrane
Abstract 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.