The plasmodium receptor for activated C kinase protein inhibits Ca(2+) signaling in mammalian cells


Autoria(s): SARTORELLO, Robson; AMAYA, Maria Jimena; NATHANSON, Michael H.; GARCIA, Celia R. S.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2009

Resumo

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. (C) 2009 Elsevier Inc. All rights reserved.

NIH[DK45710]

U.S. National Institutes of Health (NIH)

U.S. National Institutes of Health (NIH)

NIH[DK57751]

U.S. National Institutes of Health (NIH)

NIH[DK34989]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP

Identificador

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.389, n.4, p.586-592, 2009

0006-291X

http://producao.usp.br/handle/BDPI/27440

10.1016/j.bbrc.2009.09.025

http://dx.doi.org/10.1016/j.bbrc.2009.09.025

Idioma(s)

eng

Publicador

ACADEMIC PRESS INC ELSEVIER SCIENCE

Relação

Biochemical and Biophysical Research Communications

Direitos

restrictedAccess

Copyright ACADEMIC PRESS INC ELSEVIER SCIENCE

Palavras-Chave #Plasmodium falciparum #Receptor for activated C kinase #InsP3 receptors #Calcium signaling #Primary hepatocytes #INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR #HUMAN MALARIA PARASITES #PERFUSED-RAT-LIVER #HOST-CELL #TRYPANOSOMA-CRUZI #MAURERS CLEFTS #BILE SECRETION #CALCIUM #FALCIPARUM #RACK1 #Biochemistry & Molecular Biology #Biophysics
Tipo

article

original article

publishedVersion