Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum

MBio
Sabrina AbsalonJeffrey D Dvorin

Abstract

The human malaria parasite Plasmodium falciparum requires efficient egress out of an infected red blood cell for pathogenesis. This egress event is highly coordinated and is mediated by several signaling proteins, including the plant-like Pfalciparum calcium-dependent protein kinase 5 (PfCDPK5). Knockdown of PfCDPK5 results in an egress block where parasites are trapped inside their host cells. The mechanism of this PfCDPK5-dependent block, however, remains unknown. Here, we show that PfCDPK5 colocalizes with a specialized set of parasite organelles known as micronemes and is required for their discharge, implicating failure of this step as the cause of the egress defect in PfCDPK5-deficient parasites. Furthermore, we show that PfCDPK5 cooperates with the Pfalciparum cGMP-dependent kinase (PfPKG) to fully activate the protease cascade critical for parasite egress. The PfCDPK5-dependent arrest can be overcome by hyperactivation of PfPKG or by physical disruption of the arrested parasite, and we show that both treatments facilitate the release of the micronemes required for egress. Our results define the molecular mechanism of PfCDPK5 function and elucidate the complex signaling pathway of parasite egress.IMPORTANCE The signs and...Continue Reading

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Citations

Jun 9, 2020·PLoS Pathogens·Rachel M RudlaffJeffrey D Dvorin
Jul 17, 2020·Nature Communications·Aditya S PaulManoj T Duraisingh
May 18, 2019·Nature Communications·Rachel M RudlaffJeffrey D Dvorin
Jan 26, 2020·Nature Reviews. Microbiology·Joachim M MatzMichael J Blackman
Nov 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chantalle MoolmanLesetja J Legoabe
Jan 21, 2021·International Journal of Molecular Sciences·Pedro H ScarpelliCelia R S Garcia
Jan 30, 2021·Frontiers in Microbiology·Qiang ZhangYaoyu Feng
Mar 10, 2021·Journal of Cell Science·Michele S Y Tan, Michael J Blackman
Apr 23, 2021·PLoS Pathogens·Heather M KudybaVasant Muralidharan
Jun 29, 2021·Frontiers in Cellular and Infection Microbiology·Daffiny Sumam de OliveiraEdmarcia Elisa de Souza
Aug 17, 2021·Frontiers in Cellular and Infection Microbiology·Lucas Silva de OliveiraSébastien Charneau
May 18, 2018·Journal of Medicinal Chemistry·Diego González CabreraKelly Chibale

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Methods Mentioned

BETA
transgenic
PCR
genetic modifications
superresolution microscopy
transfection
flow cytometry

Software Mentioned

ZEN
Adobe Photoshop
SIM
SPOT Imaging
SR

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