TbVps41 regulates trafficking of endocytic but not biosynthetic cargo to lysosomes of bloodstream forms of Trypanosoma brucei

Srinivasan Ramakrishnan, Rodrigo P. Baptista, Beejan Asady, Guozhong Huang, Roberto Docampo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere21641
JournalFASEB Journal
Volume35
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • acidocalcisome
  • endocytosis
  • HOPS
  • lysosome
  • Trypanosoma brucei
  • Vps41

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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