Loss-of-function analyses defines vital and redundant functions of the plasmodiumrhomboid protease family

Lin, J.-W. et al. (2013) Loss-of-function analyses defines vital and redundant functions of the plasmodiumrhomboid protease family. Molecular Microbiology, 88(2), pp. 318-338. (doi:10.1111/mmi.12187)

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Abstract

Rhomboid-like proteases cleave membrane-anchored proteins within their transmembrane domains. In apicomplexan parasites substrates include molecules that function in parasite motility and host cell invasion. While two Plasmodium rhomboids, ROM1 and ROM4, have been examined, the roles of the remaining six rhomboids during the malaria parasite's life cycle are unknown. We present systematic gene deletion analyses of all eight Plasmodium rhomboid-like proteins as a means to discover stage-specific phenotypes and potential functions in the rodent malaria model, P. berghei. Four rhomboids (ROM4, 6, 7 and 8) are refractory to gene deletion, suggesting an essential role during asexual blood stage development. In contrast ROM1, 3, 9 and 10 were dispensable for blood stage development and exhibited no, subtle or severe defects in mosquito or liver development. Parasites lacking ROM9 and ROM10 showed no major phenotypic defects. Parasites lacking ROM1 presented a delay in blood stage patency following liver infection, but in contrast to a previous study blood stage parasites had similar growth and virulence characteristics as wild type parasites. Parasites lacking ROM3 in mosquitoes readily established oocysts but failed to produce sporozoites. ROM3 is the first apicomplexan rhomboid identified to play a vital role in sporogony.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Waters, Professor Andy
Authors: Lin, J.-W., Meireles, P., Prudêncio, M., Engelmann, S., Annoura, T., Sajid, M., Chevalley-Maurel, S., Ramesar, J., Nahar, C., Avramut, C.M.C., Koster, A.J., Matuschewski, K., Waters, A.P., Janse, C.J., Mair, G.R., and Khan, S.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular Microbiology
ISSN:0950-382X
ISSN (Online):1365-2958

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