title: Toxoplasma sortilin-like receptor regulates protein transport and is essential for apical secretory organelle biogenesis and host infection.
abstract: Apicomplexan parasites have an assortment of unique apical secretory organelles (rhoptries and micronemes), which have crucial functions in host infection. Here, we show that a Toxoplasma gondii sortilin-like receptor (TgSORTLR) is required for the subcellular localization and formation of apical secretory organelles. TgSORTLR is a transmembrane protein that resides within Golgi-endosomal related compartments. The lumenal domain specifically interacts with rhoptry and microneme proteins, while the cytoplasmic tail of TgSORTLR recruits cytosolic sorting machinery involved in anterograde and retrograde protein transport. Ectopic expression of the N-terminal TgSORTLR lumenal domain results in dominant negative effects with the mislocalization of both endogenous TgSORTLR as well as rhoptry and microneme proteins. Conditional ablation of TgSORTLR disrupts rhoptry and microneme biogenesis, inhibits parasite motility, and blocks both invasion into and egress from host cells. Thus, the sortilin-like receptor is essential for protein trafficking and the biogenesis of key secretory organelles in Toxoplasma.
authors.affiliation: Center for Infection and Immunity of Lille, Université Lille Nord de France, Lille, France.
authors.forename: Pierre-Julien
authors.initials: PJ
authors.lastname: Sloves
authors.forename: Stephane
authors.initials: S
authors.lastname: Delhaye
authors.forename: Thomas
authors.initials: T
authors.lastname: Mouveaux
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Werkmeister
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Agnes
authors.initials: A
authors.lastname: Hovasse
authors.forename: Tchilabalo
authors.initials: T
authors.lastname: Dilezitoko Alayi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Rajshekhar Y
authors.initials: RY
authors.lastname: Gaji
authors.forename: Christine
authors.initials: C
authors.lastname: Schaeffer-Reiss
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselear
authors.forename: Vern B
authors.initials: VB
authors.lastname: Carruthers
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D015388:Organelles / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D016019:Survival Analysis; D014122:Toxoplasma / Q000378:metabolism* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D000099183:Sortilin