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

Overview of attention for article published in Molecular Biology of the Cell, January 2015
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Title
COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A
Published in
Molecular Biology of the Cell, January 2015
DOI 10.1091/mbc.e14-06-1073
Pubmed ID
Authors

Christine A. Phillips-Krawczak, Amika Singla, Petro Starokadomskyy, Zhihui Deng, Douglas G. Osborne, Haiying Li, Christopher J. Dick, Timothy S. Gomez, Megan Koenecke, Jin-San Zhang, Haiming Dai, Luis F. Sifuentes-Dominguez, Linda N. Geng, Scott H. Kaufmann, Marco Y. Hein, Mathew Wallis, Julie McGaughran, Jozef Gecz, Bart van de Sluis, Daniel D. Billadeau, Ezra Burstein

Abstract

COMMD1 deficiency results in defective copper homeostasis but the mechanism for this has remained elusive. Herein, 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 multi-subunit 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. Altogether, 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.

Mendeley readers

The data shown below were compiled from readership statistics for 76 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 1%
United States 1 1%
Netherlands 1 1%
Unknown 73 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 28%
Researcher 20 26%
Student > Bachelor 16 21%
Student > Master 9 12%
Unspecified 7 9%
Other 8 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 34 45%
Biochemistry, Genetics and Molecular Biology 25 33%
Unspecified 8 11%
Neuroscience 4 5%
Medicine and Dentistry 4 5%
Other 6 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 November 2014.
All research outputs
#9,881,932
of 12,378,202 outputs
Outputs from Molecular Biology of the Cell
#3,487
of 3,966 outputs
Outputs of similar age
#151,688
of 227,986 outputs
Outputs of similar age from Molecular Biology of the Cell
#70
of 100 outputs
Altmetric has tracked 12,378,202 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
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