Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and post-translational modification of gliding-associated protein 45 (PfGAP45).
Plasmodium falciparum erythrocyte invasion is powered by an actin/myosin motor complex that is linked both to the tight junction and to the merozoite cytoskeleton through the Inner Membrane Complex (IMC). The IMC association of the myosin motor, PfMyoA, is maintained by its association with three proteins: PfMTIP, a myosin light chain, PfGAP45, an IMC peripheral membrane protein, and PfGAP50, an integral membrane protein of the IMC. This protein complex is referred to as the glideosome, and given its central role in erythrocyte invasion, this complex is likely the target of several specific regulatory effectors that ensure it is properly localized, assembled, and activated as the merozoite prepares to invade its target cell. However, little is known about how erythrocyte invasion as a whole is regulated, or about how or whether that regulation impacts the glideosome. Here we show that P. falciparum erythrocyte invasion is regulated by the release of intracellular calcium via the cyclic-ADP Ribose (cADPR) pathway, but that inhibition of cADPR-mediated calcium release does not affect PfGAP45 phosphorylation or glideosome association. By contrast, the serine/threonine kinase inhibitor, staurosporine, affects both PfGAP45 isoform distribution and the integrity of the glideosome complex. This data identifies specific regulatory elements involved in controlling P. falciparum erythrocyte invasion and reveals that the assembly status of the merozoite glideosome, which is central to erythrocyte invasion, is surprisingly dynamic.
Jones
Matthew L
ML
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cottingham
Chris
C
Rayner
Julian C
JC
D000818:Animals; D020013:Calcium Signaling; D004912:Erythrocytes / Q000469:parasitology*; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational
D008565:Membrane Proteins; D020033:Protein Isoforms; C509918:glideosome-associated protein 45, Plasmodium falciparum