TY - JOUR
T1 - TbVps41 regulates trafficking of endocytic but not biosynthetic cargo to lysosomes of bloodstream forms of Trypanosoma brucei
AU - Ramakrishnan, Srinivasan
AU - Baptista, Rodrigo P.
AU - Asady, Beejan
AU - Huang, Guozhong
AU - Docampo, Roberto
N1 - Funding Information:
We thank George AM Cross for BSF single marker strain, John Donelson for the p2T7 vector, Samuel Dean for pPOTv6‐blast‐blast‐mNeonGreen, James Bangs for antibodies against p67 and TbCATL, and Muthugapatti Kandasamy and the Biomedical Microscopy Core of the University of Georgia for the use of microscopes. Funding for his work was provided by the US National Institutes of Health (grant AI077538 to RD). Ti
Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - HOPS
KW - Trypanosoma brucei
KW - Vps41
KW - acidocalcisome
KW - endocytosis
KW - lysosome
UR - http://www.scopus.com/inward/record.url?scp=85106891906&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85106891906&partnerID=8YFLogxK
U2 - 10.1096/fj.202100487R
DO - 10.1096/fj.202100487R
M3 - Article
C2 - 34041791
AN - SCOPUS:85106891906
SN - 0892-6638
VL - 35
JO - FASEB Journal
JF - FASEB Journal
IS - 6
M1 - e21641
ER -