A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through ge...

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Main Authors: Robert W Moon, Cathy J Taylor, Claudia Bex, Rebecca Schepers, David Goulding, Chris J Janse, Andrew P Waters, David A Baker, Oliver Billker
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000599&type=printable
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author Robert W Moon
Cathy J Taylor
Claudia Bex
Rebecca Schepers
David Goulding
Chris J Janse
Andrew P Waters
David A Baker
Oliver Billker
author_facet Robert W Moon
Cathy J Taylor
Claudia Bex
Rebecca Schepers
David Goulding
Chris J Janse
Andrew P Waters
David A Baker
Oliver Billker
author_sort Robert W Moon
collection DOAJ
description The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP) as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta), unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta), showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.
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spelling doaj-art-0d25443adf054489a31cd3a2b84cf0582025-08-20T02:32:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-09-0159e100059910.1371/journal.ppat.1000599A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.Robert W MoonCathy J TaylorClaudia BexRebecca SchepersDavid GouldingChris J JanseAndrew P WatersDavid A BakerOliver BillkerThe ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP) as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta), unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta), showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000599&type=printable
spellingShingle Robert W Moon
Cathy J Taylor
Claudia Bex
Rebecca Schepers
David Goulding
Chris J Janse
Andrew P Waters
David A Baker
Oliver Billker
A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
PLoS Pathogens
title A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
title_full A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
title_fullStr A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
title_full_unstemmed A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
title_short A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.
title_sort cyclic gmp signalling module that regulates gliding motility in a malaria parasite
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000599&type=printable
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