TY - JOUR TI - The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors AU - Comstra, Heather S AU - McArthy, Jacob AU - Rudin-Rush, Samantha AU - Hartwig, Cortnie AU - Gokhale, Avanti AU - Zlatic, Stephanie A AU - Blackburn, Jessica B AU - Werner, Erica AU - Petris, Michael AU - D’Souza, Priya AU - Panuwet, Parinya AU - Barr, Dana Boyd AU - Lupashin, Vladimir AU - Vrailas-Mortimer, Alysia AU - Faundez, Victor A2 - West, Andrew B VL - 6 PY - 2017 DA - 2017/03/29 SP - e24722 C1 - eLife 2017;6:e24722 DO - 10.7554/eLife.24722 UR - https://doi.org/10.7554/eLife.24722 AB - 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. KW - ATP7A KW - Menkes KW - copper KW - neurodegeneration KW - neurodevelopmental KW - Golgi JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -