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

eLife

Erica Werner¹  Michael Petris²  Cortnie Hartwig³  Samantha Rudin-Rush³  Vladimir Lupashin⁴  Jessica B Blackburn⁴  Victor Faundez⁵  Heather S Comstra⁵  Avanti Gokhale⁵  Stephanie A Zlatic⁵  Parinya Panuwet⁶  Dana Boyd Barr⁶  Priya D’Souza⁶  Alysia Vrailas-Mortimer⁷  Jacob McArthy⁷ 

[1] Department of Biochemistry, Emory University, Atlanta, United States;Department of Biochemistry, University of Missouri, Columbia, United States;Department of Chemistry, Agnes Scott College, Decatur, Georgia;Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, United States;Departments of Cell Biology, Emory University, Atlanta, United States;Rollins School of Public Health, Emory University, Atlanta, United States;School of Biological Sciences, Illinois State University, Normal, United States;

关键词: ATP7A;    Menkes;    copper;    neurodegeneration;    neurodevelopmental;    Golgi;   

DOI  :  10.7554/eLife.24722

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown