Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.

The malaria parasite replicates within an intraerythrocytic parasitophorous vacuole (PV). Eventually, in a tightly regulated process called egress, proteins of the PV and intracellular merozoite surface are modified by an essential parasite serine protease called PfSUB1, whilst the enclosing PV and...

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Autores principales:	Christine R Collins, Fiona Hackett, Malcolm Strath, Maria Penzo, Chrislaine Withers-Martinez, David A Baker, Michael J Blackman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0ac5d59a497342cd85a38a3530f38e38
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spelling	oai:doaj.org-article:0ac5d59a497342cd85a38a3530f38e382021-11-18T06:05:40ZMalaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.1553-73661553-737410.1371/journal.ppat.1003344https://doaj.org/article/0ac5d59a497342cd85a38a3530f38e382013-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675297/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The malaria parasite replicates within an intraerythrocytic parasitophorous vacuole (PV). Eventually, in a tightly regulated process called egress, proteins of the PV and intracellular merozoite surface are modified by an essential parasite serine protease called PfSUB1, whilst the enclosing PV and erythrocyte membranes rupture, releasing merozoites to invade fresh erythrocytes. Inhibition of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) prevents egress, but the underlying mechanism is unknown. Here we show that PfPKG activity is required for PfSUB1 discharge into the PV, as well as for release of distinct merozoite organelles called micronemes. Stimulation of PfPKG by inhibiting parasite phosphodiesterase activity induces premature PfSUB1 discharge and egress of developmentally immature, non-invasive parasites. Our findings identify the signalling pathway that regulates PfSUB1 function and egress, and raise the possibility of targeting PfPKG or parasite phosphodiesterases in therapeutic approaches to dysregulate critical protease-mediated steps in the parasite life cycle.Christine R CollinsFiona HackettMalcolm StrathMaria PenzoChrislaine Withers-MartinezDavid A BakerMichael J BlackmanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 5, p e1003344 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Christine R Collins Fiona Hackett Malcolm Strath Maria Penzo Chrislaine Withers-Martinez David A Baker Michael J Blackman Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
description	The malaria parasite replicates within an intraerythrocytic parasitophorous vacuole (PV). Eventually, in a tightly regulated process called egress, proteins of the PV and intracellular merozoite surface are modified by an essential parasite serine protease called PfSUB1, whilst the enclosing PV and erythrocyte membranes rupture, releasing merozoites to invade fresh erythrocytes. Inhibition of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) prevents egress, but the underlying mechanism is unknown. Here we show that PfPKG activity is required for PfSUB1 discharge into the PV, as well as for release of distinct merozoite organelles called micronemes. Stimulation of PfPKG by inhibiting parasite phosphodiesterase activity induces premature PfSUB1 discharge and egress of developmentally immature, non-invasive parasites. Our findings identify the signalling pathway that regulates PfSUB1 function and egress, and raise the possibility of targeting PfPKG or parasite phosphodiesterases in therapeutic approaches to dysregulate critical protease-mediated steps in the parasite life cycle.
format	article
author	Christine R Collins Fiona Hackett Malcolm Strath Maria Penzo Chrislaine Withers-Martinez David A Baker Michael J Blackman
author_facet	Christine R Collins Fiona Hackett Malcolm Strath Maria Penzo Chrislaine Withers-Martinez David A Baker Michael J Blackman
author_sort	Christine R Collins
title	Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
title_short	Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
title_full	Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
title_fullStr	Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
title_full_unstemmed	Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
title_sort	malaria parasite cgmp-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0ac5d59a497342cd85a38a3530f38e38
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Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.

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