Ca2+ Regulation of Trypanosoma brucei Phosphoinositide Phospholipase C

Eukaryotic Cell
Sharon King-KellerSilvia N J Moreno

Abstract

We characterized a phosphoinositide phospholipase C (PI-PLC) from the procyclic form (PCF) of Trypanosoma brucei. The protein contains a domain organization characteristic of typical PI-PLCs, such as X and Y catalytic domains, an EF-hand calcium-binding motif, and a C2 domain, but it lacks a pleckstrin homology (PH) domain. In addition, the T. brucei PI-PLC (TbPI-PLC) contains an N-terminal myristoylation consensus sequence found only in trypanosomatid PI-PLCs. A peptide containing this N-terminal domain fused to green fluorescent protein (GFP) was targeted to the plasma membrane. TbPI-PLC enzymatic activity was stimulated by Ca(2+) concentrations below the cytosolic levels in the parasite, suggesting that the enzyme is constitutively active. TbPI-PLC hydrolyzes both phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2), with a higher affinity for PIP2. We found that modification of a single amino acid in the EF-hand motif greatly affected the protein's Ca(2+) sensitivity and substrate preference, demonstrating the role of this motif in Ca(2+) regulation of TbPI-PLC. Endogenous TbPI-PLC localizes to intracellular vesicles and might be using an intracellular source of PIP2. Knockdown of TbPI-PLC expression b...Continue Reading

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Citations

Jun 16, 2016·Frontiers in Immunology·Anne GeigerPhilippe Holzmuller
Mar 23, 2018·Pathogens·Srinivasan RamakrishnanRoberto Docampo
Jan 10, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Roberto Docampo, Guozhong Huang
Jan 8, 2021·ACS Chemical Biology·Brian S MantillaRoberto Docampo
Jul 4, 2021·Molecular and Biochemical Parasitology·María C Pérez-GordonesMarta Mendoza

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