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  COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A

Phillips-Krawczak, C. A., Singla, A., Starokadomskyy, P., Deng, Z., Osborne, D. G., Li, H., et al. (2015). COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. MOLECULAR BIOLOGY OF THE CELL, 26(1), 91-103. doi:10.1091/mbc.E14-06-1073.

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 Creators:
Phillips-Krawczak, Christine A.1, Author
Singla, Amika1, Author
Starokadomskyy, Petro1, Author
Deng, Zhihui1, Author
Osborne, Douglas G.1, Author
Li, Haiying1, Author
Dick, Christopher J.1, Author
Gomez, Timothy S.1, Author
Koenecke, Megan1, Author
Zhang, Jin-San1, Author
Dai, Haiming1, Author
Sifuentes-Dominguez, Luis F.1, Author
Geng, Linda N.1, Author
Kaufmann, Scott H.1, Author
Hein, Marco Y.2, Author              
Wallis, Mathew1, Author
McGaughran, Julie1, Author
Gecz, Jozef1, Author
De Sluis, Bart van1, Author
Billadeau, Daniel D.1, Author
Burstein, Ezra1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: ALDRICH SYNDROME PROTEIN, WILSON-DISEASE PROTEIN, TOXICOSIS GENE MURR1, DOMAIN-CONTAINING 1, ARP2/3 ACTIVATOR, UBIQUITIN LIGASE, CELL-LINE, RETROMER, METABOLISM, INTERACTSCell Biology; Developmental Biology;
 Abstract: COMMD1 deficiency results in defective copper homeostasis, but the mechanism for this has remained elusive. Here we report that COMMD1 is directly linked to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62. This COMMD/CCDC22/CCDC93 (CCC) complex interacts with the multisubunit WASH complex, an evolutionarily conserved system, which is required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer. Interactions between the WASH complex subunit FAM21, and the carboxyl-terminal ends of CCDC22 and CCDC93 are responsible for CCC complex recruitment to endosomes. We show that depletion of CCC complex components leads to lack of copper-dependent movement of the copper transporter ATP7A from endosomes, resulting in intracellular copper accumulation and modest alterations in copper homeostasis in humans with CCDC22 mutations. This work provides a mechanistic explanation for the role of COMMD1 in copper homeostasis and uncovers additional genes involved in the regulation of copper transporter recycling.

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Language(s): eng - English
 Dates: 2015-01
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000346923500008
DOI: 10.1091/mbc.E14-06-1073
 Degree: -

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Title: MOLECULAR BIOLOGY OF THE CELL
Source Genre: Journal
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Publ. Info: 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA : AMER SOC CELL BIOLOGY
Pages: - Volume / Issue: 26 (1) Sequence Number: - Start / End Page: 91 - 103 Identifier: ISSN: 1059-1524