L-FABP is a critical host factor for successful malaria liver stage development.
The malaria parasite liver stage produces tens of thousands of red cell-infectious forms within its host hepatocyte. It is thought that the vacuole-enclosed parasite completely depends on the host cell for successful development but the molecular parasite-host cell interactions underlying this remarkable growth have remained elusive. Using a yeast two-hybrid screen and a yeast overexpression system we show that UIS3, a parasite protein essential for liver stage development, interacts directly with liver-fatty acid binding protein, L-FABP. Down-regulation of L-FABP expression in hepatocytes severely impairs parasite growth and overexpression of L-FABP promotes growth. This is the first identified direct liver stage-host cell protein interaction, providing a possible explanation for the importance of UIS3 in liver infection.
Mikolajczak
Sebastian A
SA
Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109-5219, USA.
Jacobs-Lorena
Vanessa
V
MacKellar
Drew C
DC
Camargo
Nelly
N
Kappe
Stefan H I
SH
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D004347:Drug Interactions; D050556:Fatty Acid-Binding Proteins / Q000502:physiology*; D022781:Hepatocytes / Q000469:parasitology / Q000502:physiology; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D010967:Plasmodium yoelii / Q000254:growth & development*; D015800:Protozoan Proteins / Q000378:metabolism; D014617:Vacuoles / Q000469:parasitology
C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D015800:Protozoan Proteins