A malaria parasite formin regulates actin polymerization and localizes to the parasite-erythrocyte moving junction during invasion.
Malaria parasites invade host cells using actin-based motility, a process requiring parasite actin filament nucleation and polymerization. Malaria and other apicomplexan parasites lack Arp2/3 complex, an actin nucleator widely conserved across eukaryotes, but do express formins, another type of actin nucleator. Here, we demonstrate that one of two malaria parasite formins, Plasmodium falciparum formin 1 (PfFormin 1), and its ortholog in the related parasite Toxoplasma gondii, follows the moving tight junction between the invading parasite and the host cell, which is the predicted site of the actomyosin motor that powers motility. Furthermore, in vitro, the PfFormin1 actin-binding formin homology 2 domain is a potent nucleator, stimulating actin polymerization and, like other formins, localizing to the barbed end during filament elongation. These findings support a conserved molecular mechanism underlying apicomplexan parasite motility and, given the essential role that actin plays in cell invasion, highlight formins as important determinants of malaria parasite pathogenicity.
Baum
Jake
J
Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Tonkin
Christopher J
CJ
Paul
Aditya S
AS
Rug
Melanie
M
Smith
Brian J
BJ
Gould
Sven B
SB
Richard
Dave
D
Pollard
Thomas D
TD
Cowman
Alan F
AF
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000737:chemistry; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology*; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000737:chemistry; D014122:Toxoplasma / Q000502:physiology
D000199:Actins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins