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

Moon, R.W., Taylor, C.J., Bex, C., Schepers, R., Goulding, D., Janse, C.J., Waters, A.P., Baker, D.A. and Billker, O. (2009) A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathogens, 5(9), e1000599. (doi: 10.1371/journal.ppat.1000599)

Abstract

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 δ (PDEδ), 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 β (GCβ), showing that in ookinetes GCβ is an important source for cGMP, and that PDEδ 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.

• Item Type: Articles
• Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Waters, Professor Andy
• Authors: Moon, R.W., Taylor, C.J., Bex, C., Schepers, R., Goulding, D., Janse, C.J., Waters, A.P., Baker, D.A., and Billker, O.
• Subjects: Q Science > QR Microbiology > QR355 Virology
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Copyright Holders: © 2009 Moon et al
• First Published: First published in PLoS Pathogens 2009 5(9): e1000599
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher