A role for Toxoplasma gondii type 1 ser/thr protein phosphatase in host cell invasion.
Host cell invasion by Toxoplasma gondii tachyzoites relies on many coordinated processes. The tachyzoite participates in invasion by providing an actomyosin-dependent force driving it into the nascent parasitophorous vacuole as well as by releasing molecules which contribute to the vacuole membrane. Exposure to type 1/2A protein phosphatase inhibitors, okadaic acid (OA) or tautomycin significantly impairs tachyzoite invasiveness. Furthermore, the tachyzoite extract contains a biochemically active type 1, but not a type 2A, serine-threonine protein phosphatase, which is immunologically related to eukaryotic phosphatase type 1 catalytic subunit. When tachyzoite extracts are incubated with a monoclonal antibody reactive to human type 1 catalytic subunit, other T. gondii molecules are coprecipitated among which one competes with the inhibitory toxin OA. Finally, in vitro phosphate labelling assays indicate that the biochemically characterized PP1 activity controls the phosphorylation of several proteins. Taken together, these data strongly suggest that the type 1 phosphatase activity detected in invasive tachyzoites is implicated in the control of the host cell invasion process.
Delorme
Violaine
V
Institut Cochin de génétique moléculaire, CNRS-UPR 415, 22, rue Méchain, 75014 Paris, France.
Garcia
Alphonse
A
Cayla
Xavier
X
Tardieux
Isabelle
I
D000818:Animals; D002352:Carrier Proteins; D004722:Endoribonucleases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006790:Host-Parasite Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism; D054645:Protein Phosphatase 1; D011506:Proteins / Q000494:pharmacology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000494:pharmacology; D014122:Toxoplasma / Q000201:enzymology* / Q000472:pathogenicity*; D000097847:Protein Phosphatase Inhibitory Proteins
D002352:Carrier Proteins; D004722:Endoribonucleases; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D010762:Phosphorylase a; D054645:Protein Phosphatase 1; D011506:Proteins; D015800:Protozoan Proteins; D016601:RNA-Binding Proteins; C021042:protein phosphatase inhibitor-1; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins; C097081:PPP1R8 protein, human