Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii).
Endocytosis mechanisms are poorly known in apicomplexan parasites. Here, we show that extracellular tachyzoites of Toxoplasma gondii bind and internalize heparin-like sulfated glycans in a specific, saturable manner. Discrete binding of the glycan occurs at the anterior third of the tachyzoite, where it is rapidly concentrated inside single tubulo vesicular compartments that become multiple with time. The compound is held for several hours intracellularly with no apparent exocytosis or acidification. Incubation in the continuous presence of fluorescein isothiocyanate-conjugated heparin enhances the binding and internalization of this ligand by live tachyzoites. Two tachyzoite surface polypeptides exhibit strong binding and specificity for heparin, making them candidate receptors. Uptake of fluid-phase endocytic tracers occurs via nonspecific pinocytosis in the same region of the parasite cell, but with much lower efficiency. These observations show that extracellular tachyzoites can acquire molecules through both receptor-specific and fluid-phase endocytic mechanisms. Understanding the physiological relevance of these processes for the extracellular and intracellular stages of T. gondii may bring about direct targeting of the parasite by drug delivery into the tachyzoites.
Botero-Kleiven
S
S
Microbiology and Tumor Biology Center (MTC), Karloinska Institutet and Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Fernández
V
V
Lindh
J
J
Richter-Dahlfors
A
A
von Euler
A
A
Wahlgren
M
M
D000818:Animals; D001667:Binding, Competitive; D004705:Endocytosis / Q000502:physiology*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011134:Polysaccharides / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology*
D011134:Polysaccharides; D006493:Heparin