title: The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors.
abstract: Genetic and environmental factors, such as metals, interact to determine neurological traits. We reasoned that interactomes of molecules handling metals in neurons should include novel metal homeostasis pathways. We focused on copper and its transporter ATP7A because ATP7A null mutations cause neurodegeneration. We performed ATP7A immunoaffinity chromatography and identified 541 proteins co-isolating with ATP7A. The ATP7A interactome concentrated gene products implicated in neurodegeneration and neurodevelopmental disorders, including subunits of the Golgi-localized conserved oligomeric Golgi (COG) complex. COG null cells possess altered content and subcellular localization of ATP7A and CTR1 (SLC31A1), the transporter required for copper uptake, as well as decreased total cellular copper, and impaired copper-dependent metabolic responses. Changes in the expression of ATP7A and COG subunits inDrosophilaneurons altered synapse development in larvae and copper-induced mortality of adult flies. We conclude that the ATP7A interactome encompasses a novel COG-dependent mechanism to specify neuronal development and survival.
authors.affiliation: Departments of Cell Biology, Emory University, Atlanta, United States.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Comstra
authors.affiliation: School of Biological Sciences, Illinois State University, Normal, United States.
authors.forename: Jacob
authors.initials: J
authors.lastname: McArthy
authors.affiliation: Department of Chemistry, Agnes Scott College, Decatur, Georgia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Rudin-Rush
authors.affiliation: Department of Chemistry, Agnes Scott College, Decatur, Georgia.
authors.forename: Cortnie
authors.initials: C
authors.lastname: Hartwig
authors.affiliation: Departments of Cell Biology, Emory University, Atlanta, United States.
authors.forename: Avanti
authors.initials: A
authors.lastname: Gokhale
authors.affiliation: Departments of Cell Biology, Emory University, Atlanta, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Zlatic
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, United States.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Blackburn
authors.affiliation: Department of Biochemistry, Emory University, Atlanta, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Werner
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Petris
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, United States.
authors.forename: Priya
authors.initials: P
authors.lastname: D'Souza
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, United States.
authors.forename: Parinya
authors.initials: P
authors.lastname: Panuwet
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, United States.
authors.forename: Dana Boyd
authors.initials: DB
authors.lastname: Barr
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, United States.
authors.forename: Vladimir
authors.identifier: 0000-0002-2350-1962
authors.initials: V
authors.lastname: Lupashin
authors.affiliation: School of Biological Sciences, Illinois State University, Normal, United States.
authors.forename: Alysia
authors.initials: A
authors.lastname: Vrailas-Mortimer
authors.affiliation: Departments of Cell Biology, Emory University, Atlanta, United States.
authors.forename: Victor
authors.identifier: 0000-0002-2114-5271
authors.initials: V
authors.lastname: Faundez
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases / Q000378:metabolism*; D004330:Drosophila; D006801:Humans; D009474:Neurons / Q000502:physiology*; D060066:Protein Interaction Maps
chemical_list: D003300:Copper; D000073840:Copper-Transporting ATPases
keywords: ATP7A; D. melanogaster; Golgi; Menkes; cell biology; copper; neurodegeneration; neurodevelopmental; neuroscience