title: Paternal effect of the nuclear formin-like protein MISFIT on Plasmodium development in the mosquito vector.
abstract: Malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts. We report the discovery and characterization of MISFIT, the first protein with paternal effect on the development of the rodent malaria parasite Plasmodium berghei in Anopheles mosquitoes. MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes and ookinetes. Gene disruption results in mutant ookinetes with reduced genome content, microneme defects and altered transcriptional profiles of putative cell cycle regulators, which yet successfully invade the mosquito midgut. However, developmental arrest ensues during the ookinete transformation to oocysts leading to malaria transmission blockade. Genetic crosses between misfit mutant parasites and parasites that are either male or female gamete deficient reveal a strict requirement for a male misfit allele. MISFIT belongs to the family of formin-like proteins, which are known regulators of the dynamic remodeling of actin and microtubule networks. Our data identify the ookinete-to-oocyst transition as a critical cell cycle checkpoint in Plasmodium development and lead us to hypothesize that MISFIT may be a regulator of cell cycle progression. This study offers a new perspective for understanding the male contribution to malaria parasite development in the mosquito vector.
authors: Department of Life Sciences, Imperial College London, London, UK.
authors: Ellen S C
authors: ES
authors: Bushell
authors: Andrea
authors: A
authors: Ecker
authors: Timm
authors: T
authors: Schlegelmilch
authors: David
authors: D
authors: Goulding
authors: Gordon
authors: G
authors: Dougan
authors: Robert E
authors: RE
authors: Sinden
authors: George K
authors: GK
authors: Christophides
authors: Fotis C
authors: FC
authors: Kafatos
authors: Dina
authors: D
authors: Vlachou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D009033:Culicidae / Q000469:parasitology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005786:Gene Expression Regulation; D017125:Genes, Protozoan / Q000235:genetics; D007303:Insect Vectors / Q000469:parasitology*; D008288:Malaria / Q000635:transmission; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015800:Protozoan Proteins