Plasmodium PKG interacts with ICM1, a multi-pass membrane protein, in both asexual and sexual stages
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Plasmodium Falciparum (isolate 3d7)
DISEASE(S): Malaria
SUBMITTER: 
Steven Howell
LAB HEAD: Bram Snijders
PROVIDER: PXD020447 | Pride | 2021-02-10
REPOSITORIES: Pride
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Project description:In malaria parasites, cGMP signalling is mediated by a single cGMP-dependent protein kinase (PKG). One of the major functions of PKG is to control calcium signals essential for the parasite to exit red blood cells or for the transmission of the gametocyte stages to the mosquito. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we use pull-down approaches to identify a PKG partner protein in both Plasmodium falciparum schizonts and P. berghei gametocytes. This partner, named ICM1, is a polytopic membrane protein with homologies to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent on PKG activity. Conditional disruption of the P. falciparum ICM1 gene results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Stage-specific depletion of ICM1 in P. berghei gametocytes blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation. These results provide us with new insights into the atypical calcium homeostasis in malaria parasites
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