title: Pivotal and distinct role for Plasmodium actin capping protein alpha during blood infection of the malaria parasite.
abstract: Accurate regulation of microfilament dynamics is central to cell growth, motility and response to environmental stimuli. Stabilizing and depolymerizing proteins control the steady-state levels of filamentous (F-) actin. Capping protein (CP) binds to free barbed ends, thereby arresting microfilament growth and restraining elongation to remaining free barbed ends. In all CPs characterized to date, alpha and beta subunits form the active heterodimer. Here, we show in a eukaryotic parasitic cell that the two CP subunits can be functionally separated. Unlike the beta subunit, the CP alpha subunit of the apicomplexan parasite Plasmodium is refractory to targeted gene deletion during blood infection in the mammalian host. Combinatorial complementation of Plasmodium berghei CP genes with the orthologs from Plasmodium falciparum verified distinct activities of CP alpha and CP alpha/beta during parasite life cycle progression. Recombinant Plasmodium CP alpha could be produced in Escherichia coli in the absence of the beta subunit and the protein displayed F-actin capping activity. Thus, the functional separation of two CP subunits in a parasitic eukaryotic cell and the F-actin capping activity of CP alpha expand the repertoire of microfilament regulatory mechanisms assigned to CPs.
authors.affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, 10117, Berlin, Germany; Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA, 02115, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Ganter
authors.forename: Zaira
authors.initials: Z
authors.lastname: Rizopoulos
authors.forename: Herwig
authors.initials: H
authors.lastname: Schüler
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
mesh_terms: D051344:Actin Capping Proteins / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D020869:Gene Expression Profiling; D008288:Malaria / Q000097:blood / Q000503:physiopathology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D008840:Microfilament Proteins; D021122:Protein Subunits; D015800:Protozoan Proteins; D011994:Recombinant Proteins