TY - JOUR
T1 - COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A
AU - Phillips-Krawczak, Christine A.
AU - Singla, Amika
AU - Starokadomskyy, Petro
AU - Deng, Zhihui
AU - Osborne, Douglas G.
AU - Li, Haiying
AU - Dick, Christopher J.
AU - Gomez, Timothy S.
AU - Koenecke, Megan
AU - Zhang, Jin San
AU - Dai, Haiming
AU - Sifuentes-Dominguez, Luis F.
AU - Geng, Linda N.
AU - Kaufmann, Scott H.
AU - Hein, Marco Y.
AU - Wallis, Mathew
AU - McGaughran, Julie
AU - Gecz, Jozef
AU - Van De Sluis, Bart
AU - Billadeau, Daniel D.
AU - Burstein, Ezra
N1 - Publisher Copyright:
© 2015 Phillips-Krawczak, Singla, et al.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84920402748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920402748&partnerID=8YFLogxK
U2 - 10.1091/mbc.E14-06-1073
DO - 10.1091/mbc.E14-06-1073
M3 - Article
C2 - 25355947
AN - SCOPUS:84920402748
SN - 1059-1524
VL - 26
SP - 91
EP - 103
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 1
ER -