Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line

Harada, Masaru; Kumemura, Hiroto; Sakisaka, Shotaro; Shishido, Shoichiro; Taniguchi, Eitaro; Kawaguchi, Takumi; Hanada, Shinichiro; Koga, Hironori; Kumashiro, Ryukichi; Ueno, Takato; Suganuma, Tatsuo; Furuta, Koh; Namba, Masayoshi; Sugiyama, Toshihiro; Sata, Michio

doi:10.3892/ijmm.11.3.293

Cited by 13 publications

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“…It has been reported that the localization of ATP7B changes from the TGN to pericanalicular vesicles when the intracellular copper concentration is increased 22,23,25,26 . However, we showed that changes in copper concentration did not affect the endosome localization of ATP7B 10,13,14 . Therefore, the intracellular localization of ATP7B and its role in copper metabolism in hepatocytes has remained unclear.…”

Section: Introductionmentioning

confidence: 57%

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

Yanagimoto

Harada

Kumemura

et al. 2011

Hepatology Research

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Section: Introductionmentioning

confidence: 57%

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

Yanagimoto

Harada

Kumemura

et al. 2011

Hepatology Research

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“…Furthermore, elevation of Cu did not recruit protein from these structures, because they were still present after 4 h in 200 M Cu (data not shown). Harada et al (19,20) reported that GFP-wtATP7B expressed in either primary rat hepatocytes or Huh-7 hepatoma cells (neither polarized) showed overlap with lysosomal/endosomal markers in low Cu. These authors also observed no change in exogenous GFP-wtATP7B's distribution when intracellular Cu levels were elevated (19,20).…”

Section: The Cu-dependent Itinerary Of Atp7b In Polarized Wif-b Cellsmentioning

confidence: 98%

NH₂-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde traffic in polarized hepatic cells

Guo¹,

Nyasae²,

Braiterman³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

127

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Cu is an essential cofactor of cellular proteins but is toxic in its free state. The hepatic Cu-ATPase ATP7B has two functions in Cu homeostasis: it loads Cu+ onto newly synthesized apoceruloplasmin in the secretory pathway, thereby activating the plasma protein; and it participates in the excretion of excess Cu+ into the bile. To carry out these two functions, the membrane protein responds to changes in intracellular Cu levels by cycling between the Golgi and apical region. We used polarized hepatic WIF-B cells and high-resolution confocal microscopy to map the itinerary of endogenous and exogenous ATP7B under different Cu conditions. In Cu-depleted cells, ATP7B resided in a post-trans-Golgi network compartment that also contained syntaxin 6, whereas in Cu-loaded cells, the protein relocated to unique vesicles very near to the apical plasma membrane as well as the membrane itself. To determine the role of ATP7B's cytoplasmic NH2 terminus in regulating its intracellular movements, we generated seven mutations/deletions in this large [approximately 650 amino acid (AA)] domain and analyzed the Cu-dependent behavior of the mutant ATP7B proteins in WIF-B cells. Truncation of the ATP7B NH2 terminus up to the fifth copper-binding domain (CBD5) yielded an active ATPase that was insensitive to cellular Cu levels and constitutively trafficked to the opposite (basolateral) plasma membrane domain. Fusion of the NH2-terminal 63 AA of ATP7B to the truncated protein restored both its Cu responsiveness and correct intracellular targeting. These results indicate that important targeting information is contained in this relatively short sequence, which is absent from the related CuATPase, ATP7A.

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“…22). When environmental Cu levels are raised, ATP7B undergoes relocalization from the trans-Golgi network to vesicular structures whose exact nature has not been completely defined but which are believed to be part of the vesicular export pathway (23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Confocal Microscopic Analysis of the Interaction between Cisplatin and the Copper Transporter ATP7B in Human Ovarian Carcinoma Cells

Katano

Safaei

Samimi

et al. 2004

Clinical Cancer Research

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Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line

Cited by 13 publications

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Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

NH₂-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde traffic in polarized hepatic cells

Confocal Microscopic Analysis of the Interaction between Cisplatin and the Copper Transporter ATP7B in Human Ovarian Carcinoma Cells

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Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line

Cited by 13 publications

References 0 publications

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

NH2-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde traffic in polarized hepatic cells

Confocal Microscopic Analysis of the Interaction between Cisplatin and the Copper Transporter ATP7B in Human Ovarian Carcinoma Cells

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NH₂-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde traffic in polarized hepatic cells