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- W3175103611 abstract "Trypanosoma brucei is the causative agent of African Trypanosomiasis, a deadly disease affecting humans and cattle. There are very few drugs to treat the disease and evidence of mounting resistance raises the need for new drug development. The inositol 1,4,5 triphosphate/diacylglycerol (IP3/DAG) pathway regulates important processes in many organisms. T. brucei has an active IP3 receptor, localized to the acidocalcisome, that is essential for infection in mice. In previous work (King-Keller et al., Eukaryot. Cell 14:486–494, 2015) we characterized a phosphoinositide phospholipase C (TbPI-PLC1, Tb927.11.5970) from T. brucei that contains a domain organization characteristic of PI-PLCs, such as X and Y catalytic domains, an EF-hand calcium-binding motif, and a C2 domain, but lacks a pleckstrin homology (PH) domain. In addition, TbPI-PLC1 contains an N-terminal myristoylation consensus sequence only found in trypanosomatid PI-PLCs. Here we report the presence of a second PI-PLC-like protein (TbPI-PLC2, Tb927.6.2090) that is very similar to TbPI-PLC1 but lacks the Y catalytic domain and the C2 domain and possesses instead a PDZ domain. Recombinant TbPI-PLC2 hydrolyzes neither phosphatidylinositol (PI) nor phosphatidylinositol 4,5-bisphosphate (PIP2), and does not modulate TbPI-PLC1 activity. However, knockdown of TbPI-PLC2 expression alone or together with downregulation of TbPI-PLC1 expression by RNAi resulted in growth inhibition. This is in contrast with the lack of effect of downregulation of expression of TbPI-PLC1 alone. TbPI-PLC2 has a plasma membrane and intracellular localization and it might be involved in IP3 binding as has been reported for the phospholipase C-related catalytically inactive protein 1 (PRIP-1) of mammalian cells (Uji et al., Life Sci 72:443–453, 2002). The PDZ domain could be involved in this binding and this is being investigated. Support or Funding Information NIH grant # AI077538 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
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- W3175103611 date "2018-04-01" @default.
- W3175103611 modified "2023-09-26" @default.
- W3175103611 title "Characterization of a phospholipase C‐like protein (TbPI‐PLC2) from Trypanosoma brucei" @default.
- W3175103611 doi "https://doi.org/10.1096/fasebj.2018.32.1_supplement.533.44" @default.
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