Child_2013_Nat.Chem.Biol_9_651

Reference

Title : Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion - Child_2013_Nat.Chem.Biol_9_651
Author(s) : Child MA , Hall CI , Beck JR , Ofori LO , Albrow VE , Garland M , Bowyer PW , Bradley PJ , Powers JC , Boothroyd JC , Weerapana E , Bogyo M
Ref : Nat Chemical Biology , 9 :651 , 2013
Abstract :

Although there have been numerous advances in our understanding of how apicomplexan parasites such as Toxoplasma gondii enter host cells, many of the signaling pathways and enzymes involved in the organization of invasion mediators remain poorly defined. We recently performed a forward chemical-genetic screen in T. gondii and identified compounds that markedly enhanced infectivity. Although molecular dissection of invasion has benefited from the use of small-molecule inhibitors, the mechanisms underlying induction of invasion by small-molecule enhancers have never been described. Here we identify the Toxoplasma ortholog of human APT1, palmitoyl protein thioesterase-1 (TgPPT1), as the target of one class of small-molecule enhancers. Inhibition of this uncharacterized thioesterase triggered secretion of invasion-associated organelles, increased motility and enhanced the invasive capacity of tachyzoites. We demonstrate that TgPPT1 is a bona fide depalmitoylase, thereby establishing an important role for dynamic and reversible palmitoylation in host-cell invasion by T. gondii.

PubMedSearch : Child_2013_Nat.Chem.Biol_9_651
PubMedID: 23934245
Gene_locus related to this paper: toxgo-s4ug63

Related information

Gene_locus toxgo-s4ug63

Citations formats

Child MA, Hall CI, Beck JR, Ofori LO, Albrow VE, Garland M, Bowyer PW, Bradley PJ, Powers JC, Boothroyd JC, Weerapana E, Bogyo M (2013)
Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion
Nat Chemical Biology 9 :651

Child MA, Hall CI, Beck JR, Ofori LO, Albrow VE, Garland M, Bowyer PW, Bradley PJ, Powers JC, Boothroyd JC, Weerapana E, Bogyo M (2013)
Nat Chemical Biology 9 :651