A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites
- PMID: 16321976
- DOI: 10.1074/jbc.M509807200
A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites
Abstract
Apicomplexan parasites constitute one of the most significant groups of pathogens infecting humans and animals. The liver stage sporozoites of Plasmodium spp. and tachyzoites of Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively, use a unique mode of locomotion termed gliding motility to invade host cells and cross cell substrates. This amoeboid-like movement uses a parasite adhesin from the thrombospondin-related anonymous protein (TRAP) family and a set of proteins linking the extracellular adhesin, via an actin-myosin motor, to the inner membrane complex. The Plasmodium blood stage merozoite, however, does not exhibit gliding motility. Here we show that homologues of the key proteins that make up the motor complex, including the recently identified glideosome-associated proteins 45 and 50 (GAP40 and GAP50), are present in P. falciparum merozoites and appear to function in erythrocyte invasion. Furthermore, we identify a merozoite TRAP homologue, termed MTRAP, a micronemal protein that shares key features with TRAP, including a thrombospondin repeat domain, a putative rhomboid-protease cleavage site, and a cytoplasmic tail that, in vitro, binds the actin-binding protein aldolase. Analysis of other parasite genomes shows that the components of this motor complex are conserved across diverse Apicomplexan genera. Conservation of the motor complex suggests that a common molecular mechanism underlies all Apicomplexan motility, which, given its unique properties, highlights a number of novel targets for drug intervention to treat major diseases of humans and livestock.
Similar articles
-
TREP, a novel protein necessary for gliding motility of the malaria sporozoite.Int J Parasitol. 2009 Mar;39(4):489-96. doi: 10.1016/j.ijpara.2008.10.004. Epub 2008 Oct 25. Int J Parasitol. 2009. PMID: 19000911
-
Binding of aldolase and glyceraldehyde-3-phosphate dehydrogenase to the cytoplasmic tails of Plasmodium falciparum merozoite duffy binding-like and reticulocyte homology ligands.mBio. 2012 Sep 18;3(5):e00292-12. doi: 10.1128/mBio.00292-12. Print 2012. mBio. 2012. PMID: 22991428 Free PMC article.
-
Sites of interaction between aldolase and thrombospondin-related anonymous protein in plasmodium.Mol Biol Cell. 2003 Dec;14(12):4947-57. doi: 10.1091/mbc.e03-06-0355. Epub 2003 Oct 31. Mol Biol Cell. 2003. PMID: 14595113 Free PMC article.
-
Plasmodium falciparum aldolase and the C-terminal cytoplasmic domain of certain apical organellar proteins promote actin polymerization.Mol Biochem Parasitol. 2014 Oct;197(1-2):9-14. doi: 10.1016/j.molbiopara.2014.09.006. Epub 2014 Sep 27. Mol Biochem Parasitol. 2014. PMID: 25261592 Free PMC article. Review.
-
[The molecular mechanisms of erythrocyte invasion of Plasmodium spp. as a model organism of apicomplexan protozoa].Turkiye Parazitol Derg. 2010;34(4):203-6. doi: 10.5152/tpd.2010.15. Turkiye Parazitol Derg. 2010. PMID: 21391195 Review. Turkish.
Cited by
-
Rapid activation of distinct members of multigene families in Plasmodium spp.Commun Biol. 2020 Jul 3;3(1):351. doi: 10.1038/s42003-020-1081-3. Commun Biol. 2020. PMID: 32620892 Free PMC article.
-
Regulation of anti-Plasmodium immunity by a LITAF-like transcription factor in the malaria vector Anopheles gambiae.PLoS Pathog. 2012;8(10):e1002965. doi: 10.1371/journal.ppat.1002965. Epub 2012 Oct 18. PLoS Pathog. 2012. PMID: 23093936 Free PMC article.
-
A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components.Eukaryot Cell. 2013 Jul;12(7):1009-19. doi: 10.1128/EC.00096-13. Epub 2013 May 17. Eukaryot Cell. 2013. PMID: 23687115 Free PMC article.
-
Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito.BMC Genomics. 2013 Apr 15;14:256. doi: 10.1186/1471-2164-14-256. BMC Genomics. 2013. PMID: 23586929 Free PMC article.
-
Regulation of Plasmodium falciparum glideosome associated protein 45 (PfGAP45) phosphorylation.PLoS One. 2012;7(4):e35855. doi: 10.1371/journal.pone.0035855. Epub 2012 Apr 27. PLoS One. 2012. PMID: 22558243 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous