DOI: 10.1111/mmi.13466. Invasion of hepatocytes by <i>Plasmodium</i> sporozoites requires cGMP‐dependent protein kinase and calcium dependent protein kinase 4

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

10.1111/mmi.13466

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryInvasion 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 Ca2+, 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.

Bibliography

Govindasamy, K., Jebiwott, S., Jaijyan, D. K., Davidow, A., Ojo, K. K., Van Voorhis, W. C., Brochet, M., Billker, O., & Bhanot, P. (2016). Invasion of hepatocytes by Plasmodium sporozoites requires cGMPâdependent protein kinase and calcium dependent protein kinase 4. Molecular Microbiology, 102(2), 349â363. Portico.

Authors 9

K. Govindasamy (first)
S. Jebiwott (additional)
D. K. Jaijyan (additional)
A. Davidow (additional)
K. K. Ojo (additional)
W. C. Van Voorhis (additional)
M. Brochet (additional)
O. Billker (additional)
P. Bhanot (additional)

References 52 Referenced 70

Dates

Type	When
Created	9 years, 1 month ago (July 18, 2016, 4:44 a.m.)
Deposited	1 year, 11 months ago (Oct. 2, 2023, 6:02 a.m.)
Indexed	1 week, 2 days ago (Aug. 26, 2025, 2:44 a.m.)
Issued	9 years ago (Aug. 9, 2016)
Published	9 years ago (Aug. 9, 2016)
Published Online	9 years ago (Aug. 9, 2016)
Published Print	8 years, 11 months ago (Oct. 1, 2016)

Funders 0

None

BibTeX

@article{Govindasamy_2016, title={Invasion of hepatocytes by Plasmodium sporozoites requires cGMP‐dependent protein kinase and calcium dependent protein kinase 4}, volume={102}, ISSN={1365-2958}, url={http://dx.doi.org/10.1111/mmi.13466}, DOI={10.1111/mmi.13466}, number={2}, journal={Molecular Microbiology}, publisher={Wiley}, author={Govindasamy, K. and Jebiwott, S. and Jaijyan, D. K. and Davidow, A. and Ojo, K. K. and Van Voorhis, W. C. and Brochet, M. and Billker, O. and Bhanot, P.}, year={2016}, month=aug, pages={349–363} }

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