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Author Notes:

Email: avraila@gmail.com (AV-M) Email: vfaunde@emory.edu (VF)

HSC, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing.

JM, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review and editing.

SR-R, Data curation, Formal analysis, Investigation, Methodology, Writing—review and editing.

CH, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing—review and editing.

AG, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing—review and editing.

SAZ, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review and editing.

JBB, Conceptualization, Resources, Investigation, Methodology, Writing—review and editing.

EW, Conceptualization, Resources, Investigation, Methodology, Writing—review and editing.

MP, Resources, Investigation, Writing—review and editing.

PD’S, Resources, Formal analysis, Investigation, Writing—review and editing.

PP, Conceptualization, Resources, Formal analysis, Investigation, Writing—review and editing.

DBB, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing—review and editing.

VL, Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing.

AV-M, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing—review and editing.

VF, Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing.

We are indebted to the Faundez lab members for their comments.

We would like to thank Maria Olga Gonzalez Gonzalez for support during the manuscript figure making in Santiago, Chile and for providing mitochondria to VF.

The authors declare that no competing interests exist.

Subjects:

Research Funding:

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:

  • D. melanogaster
  • cell biology
  • neuroscience

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

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Journal Title:

eLife

Volume:

Volume 6

Publisher:

, Pages e24722-e24722

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017, Comstra et al

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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