title: A mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite Plasmodium berghei.
abstract: Differentiation of malaria parasites into sexual forms (gametocytes) in the vertebrate host and their subsequent development into gametes in the mosquito vector are crucial steps in the completion of the parasite's life cycle and transmission of the disease. The molecular mechanisms that regulate the sexual cycle are poorly understood. Although several signal transduction pathways have been implicated, a clear understanding of the pathways involved has yet to emerge. Here, we show that a Plasmodium berghei homologue of Plasmodium falciparum mitogen-activated kinase-2 (Pfmap-2), a gametocyte-specific mitogen-activated protein kinase (MAPK), is required for male gamete formation. Parasites lacking Pbmap-2 are competent for gametocytogenesis, but exflagellation of male gametocytes, the process that leads to male gamete formation, is almost entirely abolished in mutant parasites. Consistent with this result, transmission of mutant parasites to mosquitoes is grossly impaired. This finding identifies a crucial role for a MAPK pathway in malaria transmission.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Rangarajan
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.forename: Deepa
authors.initials: D
authors.lastname: Jethwaney
authors.forename: Priscilla
authors.initials: P
authors.lastname: Maldonado
authors.forename: Dominique
authors.initials: D
authors.lastname: Dorin
authors.forename: Ali A
authors.initials: AA
authors.lastname: Sultan
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D003001:Cloning, Molecular; D005260:Female; D005407:Flagella / Q000502:physiology; D005718:Gametogenesis / Q000235:genetics / Q000502:physiology*; D006790:Host-Parasite Interactions; D007303:Insect Vectors; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008288:Malaria / Q000469:parasitology / Q000635:transmission; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000502:physiology*; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D019950:Mitogen-Activated Protein Kinase 1