title: A family of transmembrane microneme proteins of Toxoplasma gondii contain EGF-like domains and function as escorters.
abstract: TgMIC6, TgMIC7, TgMIC8 and TgMIC9 are members of a novel family of transmembrane proteins localized in the micronemes of the protozoan parasite Toxoplasma gondii. These proteins contain multiple epidermal growth factor-like domains, a putative transmembrane spanning domain and a short cytoplasmic tail. Sorting signals to the micronemes are encoded in this short tail. We established previously that TgMIC6 serves as an escorter for two soluble adhesins, TgMIC1 and TgMIC4. Here, we present the characterization of TgMIC6 and three additional members of this family, TgMIC7, -8 and -9. Consistent with having sorting signals localized in its C-terminal tail, TgMIC6 exhibits a classical type I membrane topology during its transport along the secretory pathway and during storage in the micronemes. TgMIC6 is processed at the N-terminus, probably in the trans-Golgi network, and the cleavage site has been precisely mapped. Additionally, like other members of the thrombospondin-related anonymous protein family, TgMIC2, TgMIC6 and TgMIC8 are proteolytically cleaved near their C-terminal domain upon discharge by micronemes. We also provide evidence that TgMIC8 escorts another recently described soluble adhesin, TgMIC3. This suggests that the existence of microneme protein complexes is not an exception but rather the rule. TgMIC6 and TgMIC8 are expressed in the rapidly dividing tachyzoites, while TgMIC7 and TgMIC9 genes are predominantly expressed in bradyzoites, where they presumably also serve as escorters.
authors.affiliation: Imperial College of Science, Technology and Medicine, Department of Biology, Sir Alexander Fleming Building, Imperial College Road, London, SW7 2AZ, UK.
authors.forename: Markus
authors.initials: M
authors.lastname: Meissner
authors.forename: Matthias
authors.initials: M
authors.lastname: Reiss
authors.forename: Nicola
authors.initials: N
authors.lastname: Viebig
authors.forename: Vern B
authors.initials: VB
authors.lastname: Carruthers
authors.forename: Catherine
authors.initials: C
authors.lastname: Toursel
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
authors.forename: James W
authors.initials: JW
authors.lastname: Ajioka
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014122:Toxoplasma / Q000166:cytology / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D002352:Carrier Proteins; C408878:MIC2 protein, Toxoplasma gondii; C421382:MIC3 protein, Toxoplasma gondii; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor