title: Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion.
abstract: The advent of techniques to study palmitoylation on a whole proteome scale has revealed that it is an important reversible modification that plays a role in regulating multiple biological processes. Palmitoylation can control the affinity of a protein for lipid membranes, which allows it to impact protein trafficking, stability, folding, signalling and interactions. The publication of the palmitome of the schizont stage of Plasmodium falciparum implicated a role for palmitoylation in host cell invasion, protein export and organelle biogenesis. However, nothing is known so far about the repertoire of protein S-acyl transferases (PATs) that catalyse this modification in Apicomplexa. We undertook a comprehensive analysis of the repertoire of Asp-His-His-Cys cysteine-rich domain (DHHC-CRD) PAT family in Toxoplasma gondii and Plasmodium berghei by assessing their localization and essentiality. Unlike functional redundancies reported in other eukaryotes, some apicomplexan-specific DHHCs are essential for parasite growth, and several are targeted to organelles unique to this phylum. Of particular interest is DHHC7, which localizes to rhoptry organelles in all parasites tested, including the major human pathogen P. falciparum. TgDHHC7 interferes with the localization of the rhoptry palmitoylated protein TgARO and affects the apical positioning of the rhoptry organelles. This PAT has a major impact on T. gondii host cell invasion, but not on the parasite's ability to egress.
authors: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Rue Michel-Servet 1, CH-1211, Geneva 4, Switzerland.
authors: Karine
authors: K
authors: Frénal
authors: Chwen L
authors: CL
authors: Tay
authors: Christina
authors: C
authors: Mueller
authors: Ellen S
authors: ES
authors: Bushell
authors: Yonggen
authors: Y
authors: Jia
authors: Arnault
authors: A
authors: Graindorge
authors: Oliver
authors: O
authors: Billker
authors: Julian C
authors: JC
authors: Rayner
authors: Dominique
authors: D
authors: Soldati-Favre
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D018929:Cell Culture Techniques; D017353:Gene Deletion; D018503:Genome, Protozoan; D006801:Humans; D010802:Phylogeny; D010962:Plasmodium berghei / Q000201:enzymology* / Q000472:pathogenicity; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000201:enzymology* / Q000472:pathogenicity
chemical_list: D015800:Protozoan Proteins; D000123:Acetyltransferases; C062782:protein acyltransferase
keywords: Apicomplexa; Plasmodium berghei; Plasmodium falciparum; Toxoplasma gondii; egress; invasion; palmitoyl acyl transferase; palmitoylation; rhoptry organelle
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