The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors.

• Type of Material: Article
• Authors: Heather Comstra, Emory University; Jacob McArthy McArthy, Illinois State University; Samantha Rudin-Rush, Agnes Scott College; Cortnie Hartwig, Agnes Scott College; Avanti Gokhale, Emory University; Stephanie A Zlatic, Emory University; Jessica B Blackburn, University of Arkansas for Medical Sciences; Erica Werner, Emory University; Michael Petris, University of Missouri; Priya D'Souza, Emory University; Parinya Panuwet, Emory University; Dana Barr, Emory University; Vladimir Lupashin, University of Arkansas for Medical Sciences; Alysia Vrailas-Mortimer, llinois State University; Victor Faundez, Emory University
• Language: English
• Date: 2017-03-29
• Publisher: eLife Sciences Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2017, Comstra et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.24722
• Title of Journal or Parent Work: eLife
• ISSN: 2050-084X
• Volume: 6
• Start Page: e24722
• End Page: e24722
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health: NS088503 to VF, DK093386 to MP, GM083144 to VL, and the HERCULES grant (NIEHS: P30 ES019776).; Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. SR-R was supported by a fellowship from the Marion T.
• Keywords: neuroscience; D. melanogaster; cell biology
• Research Categories: Biology, Genetics; Chemistry, Biochemistry; Biology, Neuroscience

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 in Drosophila neurons 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.