RRC ID 18930
Author Miyayama T, Hiraoka D, Kawaji F, Nakamura E, Suzuki N, Ogra Y.
Title Roles of COMM-domain-containing 1 in stability and recruitment of the copper-transporting ATPase in a mouse hepatoma cell line.
Journal Biochem. J.
Abstract A novel function of COMMD1 {COMM [copper metabolism MURR1 (mouse U2af1-rs1 region 1)]-domain-containing 1}, a protein relevant to canine copper toxicosis, was examined in the mouse hepatoma cell line Hepa 1-6 with multi-disciplinary techniques consisting of molecular and cellular biological techniques, speciation and elemental imaging. To clarify the function of COMMD1, COMMD1-knockdown was accomplished by introducing siRNA (small interfering RNA) into the cells. Although COMMD1-knockdown did not affect copper incorporation, it inhibited copper excretion, resulting in copper accumulation, which predominantly existed in the form bound to MT (metallothionein). It is known that the liver copper transporter Atp7b (ATP-dependent copper transporter 7beta), localizes on the trans-Golgi network membrane under basal copper conditions and translocates to cytoplasmic vesicles to excrete copper when its concentration exceeds a certain threshold, with the vesicles dispersing in the periphery of the cell. COMMD1-knockdown reduced the expression of Atp7b, and abolished the relocation of Atp7b back from the periphery to the trans-Golgi network membrane when the copper concentration was reduced by treatment with a Cu(I) chelator. The same phenomena were observed during COMMD1-knockdown when another Atp7b substrate, cis-diamminedichloroplatinum, and its sequestrator, glutathione ethylester, were applied. These results suggest that COMMD1 maintains the amount of Atp7b and facilitates recruitment of Atp7b from cytoplasmic vesicles to the trans-Golgi network membrane, i.e. COMMD1 is required to shuttle Atp7b when the intracellular copper level returns below the threshold.
Volume 429(1)
Pages 53-61
Published 2010-7-1
DOI 10.1042/BJ20100223
PII BJ20100223
PMID 20433422
MeSH Adaptor Proteins, Signal Transducing Adenosine Triphosphatases / metabolism* Animals Carcinoma, Hepatocellular / enzymology Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Cation Transport Proteins / metabolism* Cell Line, Tumor Copper / chemistry Copper / deficiency Copper / metabolism Copper-transporting ATPases Enzyme Stability / genetics Gene Knockdown Techniques / methods Intracellular Fluid / chemistry Intracellular Fluid / enzymology Intracellular Fluid / metabolism Liver Neoplasms / enzymology Liver Neoplasms / genetics Liver Neoplasms / metabolism* Mice Proteins / antagonists & inhibitors Proteins / genetics Proteins / physiology* RNA, Small Interfering / genetics
IF 3.857
Times Cited 22
Human and Animal Cells Hepa 1-6 (RCB1638)