title: Protein trafficking abnormalities in Drosophila tissues with impaired activity of the ZIP7 zinc transporter Catsup.
abstract: Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of the Notch signaling pathway is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is crucial for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila epithelial tissues, we recovered mutations that disrupt the Catsup gene, which encodes the Drosophila ortholog of the mammalian ZIP7 zinc transporter. Loss of Catsup function causes Notch to accumulate abnormally in the endoplasmic reticulum (ER) and Golgi compartments, resulting in impaired Notch signaling. In addition, Catsup mutant cells exhibit elevated ER stress, suggesting that impaired zinc homeostasis causes increased levels of misfolded proteins within the secretory compartment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Casper
authors.initials: C
authors.lastname: Groth
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasamura
authors.forename: Mansi R
authors.initials: MR
authors.lastname: Khanna
authors.forename: Michael
authors.initials: M
authors.lastname: Whitley
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fortini
mesh_terms: D000818:Animals; D017209:Apoptosis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D060227:Imaginal Discs / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism; D055571:Secretory Pathway; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology; D015032:Zinc / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C511455:catsup protein, Drosophila; D015032:Zinc
keywords: Drosophila; Notch; Protein trafficking; Secretory pathway; Zinc transporter