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Invasion of hepatocytes by Plasmodium sporozoites requires cGMP-dependent protein kinase and calcium dependent protein kinase 4.

Authors :
Govindasamy K
Jebiwott S
Jaijyan DK
Davidow A
Ojo KK
Van Voorhis WC
Brochet M
Billker O
Bhanot P
Source :
Molecular microbiology [Mol Microbiol] 2016 Oct; Vol. 102 (2), pp. 349-363. Date of Electronic Publication: 2016 Aug 09.
Publication Year :
2016

Abstract

Invasion of hepatocytes by sporozoites is essential for Plasmodium to initiate infection of the mammalian host. The parasite's subsequent intracellular differentiation in the liver is the first developmental step of its mammalian cycle. Despite their biological significance, surprisingly little is known of the signalling pathways required for sporozoite invasion. We report that sporozoite invasion of hepatocytes requires signalling through two second-messengers - cGMP mediated by the parasite's cGMP-dependent protein kinase (PKG), and Ca <superscript>2+</superscript> , mediated by the parasite's calcium-dependent protein kinase 4 (CDPK4). Sporozoites expressing a mutated form of Plasmodium berghei PKG or carrying a deletion of the CDPK4 gene are defective in invasion of hepatocytes. Using specific and potent inhibitors of Plasmodium PKG and CDPK4, we demonstrate that PKG and CDPK4 are required for sporozoite motility, and that PKG regulates the secretion of TRAP, an adhesin that is essential for motility. Chemical inhibition of PKG decreases parasite egress from hepatocytes by inhibiting either the formation or release of merosomes. In contrast, genetic inhibition of CDPK4 does not significantly decrease the number of merosomes. By revealing the requirement for PKG and CDPK4 in Plasmodium sporozoite invasion, our work enables a better understanding of kinase pathways that act in different Plasmodium stages.<br /> (© 2016 John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1365-2958
Volume :
102
Issue :
2
Database :
MEDLINE
Journal :
Molecular microbiology
Publication Type :
Academic Journal
Accession number :
27425827
Full Text :
https://doi.org/10.1111/mmi.13466