TY - JOUR
T1 - An X-Domain Phosphoinositide Phospholipase C (PI-PLC-like) of Trypanosoma brucei Has a Surface Localization and Is Essential for Proliferation
AU - Negrão, Núria W.
AU - Crowe, Logan P.
AU - Mantilla, Brian S.
AU - Baptista, Rodrigo P.
AU - King-Keller, Sharon
AU - Huang, Guozhong
AU - Docampo, Roberto
N1 - Funding Information:
This work was funded by the U.S. National Institutes of Health (Grant AI077538 to R.D.). B.S.M. is supported by the UKRI Grand Challenges Research Fund (A Global Network for Neglected Tropical Diseases, grant MR/P027989/1). L.P.C. was supported by the U.S. National Institute of Health (Training Grant T32 AI060546).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2/28
Y1 - 2023/2/28
N2 - Trypanosoma brucei is the causative agent of African trypanosomiasis, a deadly disease that affects humans and cattle. There are very few drugs to treat it, and there is evidence of mounting resistance, raising the need for new drug development. Here, we report the presence of a phosphoinositide phospholipase C (TbPI-PLC-like), containing an X and a PDZ domain, that is similar to the previously characterized TbPI-PLC1. TbPI-PLC-like only possesses the X catalytic domain and does not have the EF-hand, Y, and C2 domains, having instead a PDZ domain. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity in vitro. TbPI-PLC-like shows a plasma membrane and intracellular localization in permeabilized cells and a surface localization in non-permeabilized cells. Surprisingly, knockdown of TbPI-PLC-like expression by RNAi significantly affected proliferation of both procyclic and bloodstream trypomastigotes. This is in contrast with the lack of effect of downregulation of expression of TbPI-PLC1.
AB - Trypanosoma brucei is the causative agent of African trypanosomiasis, a deadly disease that affects humans and cattle. There are very few drugs to treat it, and there is evidence of mounting resistance, raising the need for new drug development. Here, we report the presence of a phosphoinositide phospholipase C (TbPI-PLC-like), containing an X and a PDZ domain, that is similar to the previously characterized TbPI-PLC1. TbPI-PLC-like only possesses the X catalytic domain and does not have the EF-hand, Y, and C2 domains, having instead a PDZ domain. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity in vitro. TbPI-PLC-like shows a plasma membrane and intracellular localization in permeabilized cells and a surface localization in non-permeabilized cells. Surprisingly, knockdown of TbPI-PLC-like expression by RNAi significantly affected proliferation of both procyclic and bloodstream trypomastigotes. This is in contrast with the lack of effect of downregulation of expression of TbPI-PLC1.
KW - Phospholipase C
KW - RNA interference
KW - Trypanosoma brucei
KW - plasma membrane
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U2 - 10.3390/pathogens12030386
DO - 10.3390/pathogens12030386
M3 - Article
C2 - 36986308
AN - SCOPUS:85151475354
SN - 2076-0817
VL - 12
JO - Pathogens
JF - Pathogens
IS - 3
M1 - 386
ER -