title: AP-1 in Toxoplasma gondii mediates biogenesis of the rhoptry secretory organelle from a post-Golgi compartment.
abstract: We have previously demonstrated that Toxoplasma gondii has a tyrosine-based sorting system, which mediates protein targeting to the lysosome-like rhoptry secretory organelle. We now show that rhoptry protein targeting is also dependent on a dileucine motif and occurs from a post-Golgi endocytic organelle to mature rhoptries in an adaptin-dependent fashion. The T. gondii AP-1 adaptin complex is implicated in this transport because the micro1 chain of T. gondii AP-1 (a) was localized to multivesicular endosomes and the limiting and luminal membranes of the rhoptries; (b) bound to endocytic tyrosine motifs in rhoptry proteins, but not in proteins from dense granule secretory organelles; (c) when mutated in predicted tyrosine-binding motifs, led to accumulation of the rhoptry protein ROP2 in a post-Golgi multivesicular compartment; and (d) when depleted via antisense mRNA, resulted in accumulation of multivesicular endosomes and immature rhoptries. These are the first results to implicate AP-1 in transport from a post-Golgi compartment to a mature secretory organelle and substantially expand the role for AP-1 in anterograde protein transport.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8022, USA.
authors.forename: Huân M
authors.initials: HM
authors.lastname: Ngô
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Kerstin
authors.initials: K
authors.lastname: Paprotka
authors.forename: Marc
authors.initials: M
authors.lastname: Pypaert
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hoppe
authors.forename: Keith A
authors.initials: KA
authors.lastname: Joiner
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D006056:Golgi Apparatus / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000502:physiology; D015800:Protozoan Proteins / Q000502:physiology*; D022142:Secretory Vesicles / Q000502:physiology* / Q000648:ultrastructure; D016415:Sequence Alignment; D014122:Toxoplasma / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: D033961:Adaptor Protein Complex 1; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090555:ROP 2 protein, Toxoplasma gondii