{"doi":"10.1091/mbc.e14-06-1073","title":"COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A","abstract":"<jats:p> 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. </jats:p>","journal":"Molecular Biology of the Cell","year":2015,"id":24035,"datarank":6.581834525368455,"base_score":5.501258210544727,"endowment":5.501258210544727,"self_citation_contribution":0.8251887315817092,"citation_network_contribution":5.7566457937867455,"self_endowment_contribution":0.8251887315817092,"citer_contribution":5.7566457937867455,"corpus_percentile":null,"corpus_rank":null,"citation_count":244,"citer_count":200,"citers_with_citation_signal":182,"citers_with_endowment":182,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":145461,"name":"Amika Singla","orcid":null,"position":1,"is_corresponding":false},{"id":145462,"name":"Petro Starokadomskyy","orcid":null,"position":2,"is_corresponding":false},{"id":145463,"name":"Zhihui Deng","orcid":null,"position":3,"is_corresponding":false},{"id":145464,"name":"Douglas G. 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