title: An ancient protein phosphatase, SHLP1, is critical to microneme development in Plasmodium ookinetes and parasite transmission.
abstract: Signaling pathways controlled by reversible protein phosphorylation (catalyzed by kinases and phosphatases) in the malaria parasite Plasmodium are of great interest, for both increased understanding of parasite biology and identification of novel drug targets. Here, we report a functional analysis in Plasmodium of an ancient bacterial Shewanella-like protein phosphatase (SHLP1) found only in bacteria, fungi, protists, and plants. SHLP1 is abundant in asexual blood stages and expressed at all stages of the parasite life cycle. shlp1 deletion results in a reduction in ookinete (zygote) development, microneme formation, and complete ablation of oocyst formation, thereby blocking parasite transmission. This defect is carried by the female gamete and can be rescued by direct injection of mutant ookinetes into the mosquito hemocoel, where oocysts develop. This study emphasizes the varied functions of SHLP1 in Plasmodium ookinete biology and suggests that it could be a novel drug target for blocking parasite transmission.
authors: Centre for Genetics and Genomics, School of Biology, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors: Eva-Maria
authors: EM
authors: Patzewitz
authors: David S
authors: DS
authors: Guttery
authors: Benoit
authors: B
authors: Poulin
authors: Chandra
authors: C
authors: Ramakrishnan
authors: David J P
authors: DJ
authors: Ferguson
authors: Richard J
authors: RJ
authors: Wall
authors: Declan
authors: D
authors: Brady
authors: Anthony A
authors: AA
authors: Holder
authors: Balázs
authors: B
authors: Szöőr
authors: Rita
authors: R
authors: Tewari
mesh_terms: D000595:Amino Acid Sequence; D017353:Gene Deletion; D005854:Germ Cells / Q000201:enzymology; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010962:Plasmodium berghei / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D033761:Spores, Protozoan / Q000201:enzymology / Q000254:growth & development; D014774:Virulence / Q000235:genetics; D015053:Zygote / Q000201:enzymology
chemical_list: D015800:Protozoan Proteins; D010749:Phosphoprotein Phosphatases