The plasmodium receptor for activated C kinase protein inhibits Ca(2+) signaling in mammalian cells.
Plasmodium falciparum, the most lethal malarial parasite, expresses an ortholog for the protein kinase C (PKC) activator RACK1. However, PKC has not been identified in this parasite, and the mammalian RACK1 can interact with the inositol 1,4,5-trisphosphate receptor (InsP3R). Therefore we investigated whether the Plasmodium ortholog PfRACK also can affect InsP3R-mediated Ca(2+) signaling in mammalian cells. GFP-tagged PfRACK and endogenous RACK1 were expressed in a similar distribution within cells. PfRACK inhibited agonist-induced Ca(2+) signals in cells expressing each isoform of the InsP3R, and this effect persisted when expression of endogenous RACK1 was reduced by siRNA. PfRACK also inhibited Ca(2+) signals induced by photorelease of caged InsP3. These findings provide evidence that PfRACK directly inhibits InsP3-mediated Ca(2+) signaling in mammalian cells. Interference with host cell signaling pathways to subvert the host intracellular milieu may be an important mechanism for parasite survival.
Sartorello
Robson
R
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. sartorello@gmail.com
Amaya
Maria Jimena
MJ
Nathanson
Michael H
MH
Garcia
Célia R S
CR
D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface