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

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 remainin...

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Main Authors: Lin, Jing-wen (Author) , Meireles, Patrícia (Author) , Prudêncio, Miguel (Author) , Engelmann, Sabine (Author) , Annoura, Takeshi (Author) , Sajid, Mohammed (Author) , Chevalley-Maurel, Séverine (Author) , Ramesar, Jai (Author) , Nahar, Carolin (Author) , Avramut, Cristina M. C. (Author) , Koster, Abraham J. (Author) , Matuschewski, Kai (Author) , Waters, Andrew P. (Author) , Janse, Chris J. (Author) , Mair, Gunnar R. (Author) , Khan, Shahid M. (Author)
Format: Article (Journal)
Language:English
Published: 12 March 2013
In: Molecular microbiology
Year: 2013, Volume: 88, Issue: 2, Pages: 318-338
ISSN:1365-2958
DOI:10.1111/mmi.12187
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/mmi.12187
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/mmi.12187
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Author Notes:Jing-wen Lin, Patrícia Meireles, Miguel Prudêncio, Sabine Engelmann, Takeshi Annoura, Mohammed Sajid, Séverine Chevalley-Maurel, Jai Ramesar, Carolin Nahar, Cristina M.C. Avramut, Abraham J. Koster, Kai Matuschewski, Andrew P. Waters, Chris J. Janse, Gunnar R. Mair and Shahid M. Khan
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Summary: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 Description:Gesehen am 08.03.2022
Physical Description:Online Resource
ISSN:1365-2958
DOI:10.1111/mmi.12187