title: Novel insights into the composition and function of the Toxoplasma IMC sutures.
abstract: The Toxoplasma inner membrane complex (IMC) is a specialized organelle underlying the parasite's plasma membrane that consists of flattened rectangular membrane sacs that are sutured together and positioned atop a supportive cytoskeleton. We have previously identified a novel class of proteins localizing to the transverse and longitudinal sutures of the IMC, which we named IMC sutures components (ISCs). Here, we have used proximity-dependent biotin identification at the sutures to better define the composition of this IMC subcompartment. Using ISC4 as bait, we demonstrate biotin-dependent labeling of the sutures and have uncovered two new ISCs. We also identified five new proteins that exclusively localize to the transverse sutures that we named transverse sutures components (TSCs), demonstrating that components of the IMC sutures consist of two groups: those that localize to the transverse and longitudinal sutures (ISCs) and those residing only in the transverse sutures (TSCs). In addition, we functionally analyze the ISC protein ISC3 and demonstrate that ISC3-null parasites have morphological defects and reduced fitness in vitro. Most importantly, Δisc3 parasites exhibit a complete loss of virulence in vivo. These studies expand the known composition of the IMC sutures and highlight the contribution of ISCs to the ability of the parasite to proliferate and cause disease.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Andy S
authors.initials: AS
authors.lastname: Moon
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Hannah N
authors.initials: HN
authors.lastname: Bell
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Huang
authors.affiliation: Department of Biological Chemistry and Institute of Genomics and Proteomics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Justin Y
authors.initials: JY
authors.lastname: Toh
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Lin
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Santhosh M
authors.initials: SM
authors.lastname: Nadipuram
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Elliot W
authors.initials: EW
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Choi
authors.affiliation: Department of Biological Chemistry and Institute of Genomics and Proteomics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bradley
mesh_terms: D002478:Cells, Cultured; D005260:Female; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions; D006801:Humans; D010711:Phosphatidate Phosphatase / Q000502:physiology / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000502:physiology* / Q000648:ultrastructure; D014122:Toxoplasma / Q000502:physiology / Q000648:ultrastructure*; D014774:Virulence
chemical_list: D015800:Protozoan Proteins; D010711:Phosphatidate Phosphatase