Functional characterization of both MAP kinases of the human malaria parasite Plasmodium falciparum by reverse genetics.
Details
Serval ID
serval:BIB_6CB6EE5D624F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional characterization of both MAP kinases of the human malaria parasite Plasmodium falciparum by reverse genetics.
Journal
Molecular Microbiology
ISSN
0950-382X (Print)
ISSN-L
0950-382X
Publication state
Published
Issued date
09/2007
Volume
65
Number
5
Pages
1170-1180
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The kinome of the human malaria parasite Plasmodium falciparum includes two genes encoding mitogen-activated protein kinase (MAPK) homologues, pfmap-1 and pfmap-2, but no clear orthologue of the MAPK kinase (MAPKK) family, raising the question of the mode of activation and function of the plasmodial MAPKs. Functional studies in the rodent malaria model Plasmodium berghei recently showed the map-2 gene to be dispensable for asexual growth and gametocytogenesis, but essential for male gametogenesis in the mosquito vector. Here, we demonstrate by using a reverse genetics approach that the map-2 gene is essential for completion of the asexual cycle of P. falciparum, an unexpected result in view of the non-essentiality of the orthologous gene for P. berghei erythrocytic schizogony. This validates Pfmap-2 as a potential target for chemotherapeutic intervention. In contrast, the other P. falciparum MAPK, Pfmap-1, is required neither for in vitro schizogony and gametocytogenesis in erythrocytes, nor for gametogenesis and sporogony in the mosquito vector. However, Pfmap-2 protein levels are elevated in pfmap-1(-) parasites, suggesting that Pfmap-1 fulfils an important function in asexual parasites that necessitates compensatory adaptation in parasites lacking this enzyme.
Keywords
Animals, Anopheles gambiae/parasitology, Erythrocytes/parasitology, Female, Humans, Isoenzymes/genetics, Isoenzymes/metabolism, Malaria, Falciparum, Male, Mitogen-Activated Protein Kinases/genetics, Mitogen-Activated Protein Kinases/metabolism, Phenotype, Plasmodium falciparum/enzymology, Plasmodium falciparum/physiology, Protozoan Proteins/genetics, Protozoan Proteins/metabolism
Pubmed
Open Access
Yes
Create date
15/01/2014 13:38
Last modification date
20/01/2021 7:26