Clusterin and COMMD1 Independently Regulate Degradation of the Mammalian Copper ATPases ATP7A and ATP7B

Materia, Stephanie; Cater, Michael A.; Klomp, Leo W. J.; Mercer, Julian F. B.; Fontaine, Sharon La

doi:10.1074/jbc.m111.302216

Cited by 79 publications

(80 citation statements)

References 68 publications

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“…Clusterin has been found to work as a chaperone that regulates the turnover of copper ATPases that are central to brain copper homeostasis [384], as shown in several neurological diseases but perhaps best in Wilson's disease where mutations in these copper proteins directly cause disease [385]. Such mutations have indeed recently been related to ApoE4, as carriers of this isoform show earlier onset of Wilson's disease [386].…”

Section: The Role Of Apolipoproteins In Copper/zinc Homeostasismentioning

confidence: 97%

Alzheimer’s disease due to loss of function: A new synthesis of the available data

Kepp

2016

Progress in Neurobiology

117

107

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Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses. The amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease. Here, a new loss-of-function hypothesis is synthesized that accounts for the anomalies of the amyloid hypothesis, e.g. the curious pathogenicity of the Aβ42/Aβ40 ratio, the loss of Aβ caused by presenilin mutation, the mixed phenotypes of APP mutations, the poor clinical-biochemical correlations for genetic variant carriers, and the failure of Aβ reducing drugs. The amyloid-loss view accounts for recent findings on the structure and chemical features of Aβ variants and their coupling to human patient data. The lost normal function of APP/Aβ is argued to be metal transport across neuronal membranes, a view with no apparent anomalies and substantially more explanatory power than the gain-of-function amyloid hypothesis. In the loss-of-function scenario, the central event of Aβ aggregation is interpreted as a loss of soluble, functional monomer Aβ rather than toxic overload of oligomers. Accordingly, new research models and treatment strategies should focus on remediation of the functional amyloid balance, rather than strict containment of Aβ, which, for reasons rationalized in this review, has failed clinically.

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Section: The Role Of Apolipoproteins In Copper/zinc Homeostasismentioning

confidence: 97%

Alzheimer’s disease due to loss of function: A new synthesis of the available data

Kepp

2016

Progress in Neurobiology

117

107

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“…Loss of COMMD1 has been correlated to disruption of ion transporters, including ␦-epithelial Na channel (␦ENaC) and hepatic Cu transport (2,29,56). To examine constitutive downregulation of COMMD1 in epithelial cells, we obtained two HT29 stable colonic cell lines, one with siCOMMD1-vector and the Fig.…”

Section: Constitutive Downregulation Of Commd1 Reduces Basolateral Mementioning

confidence: 99%

COMMD1 interacts with the COOH terminus of NKCC1 in Calu-3 airway epithelial cells to modulate NKCC1 ubiquitination

Smith

Litman

Liedtke

2013

American Journal of Physiology-Cell Physiology

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Smith L, Litman P, Liedtke CM. COMMD1 interacts with the COOH terminus of NKCC1 in Calu-3 airway epithelial cells to modulate NKCC1 ubiquitination. Am J Physiol Cell Physiol 305: C133-C146, 2013. First published March 20, 2013 doi:10.1152/ajpcell.00394.2012.-Mice deficient in Na-K-2Cl cotransporter (NKCC1) have been generated by targeted disruption of the gene encoding NKCC1 involving the carboxy terminus (CT-NKCC1) but not the amino terminus. We hypothesize that the resulting physiological defects are due to loss of proteins interacting with CT-NKCC1. Using a yeast two-hybrid approach, adaptor protein COMMD1 was found to bind to CT-NKCC1 (aa 1,040 -1,212). Binding was verified in a yeast-independent system using GST-COMMD1 and myc-CT-NKCC1. Truncated COMMD1 and CT-NKCC1 peptides were used in binding assays to identify the site of interaction. The results demonstrate concentration-dependent binding of COMMD1 (aa 1-47) to CT-NKCC1 (aa 1,040 -1,134). Endogenous COMMD1 was detected in pull downs using recombinant FLAG-CT-NKCC1; this co-pull down was blocked by COMMD1 (aa 1-47). CT-NKCC1 (aa 1,040 -1,137) decreased basolateral membrane expression of NKCC1, and COMMD1 (aa 1-47) increased NKCC1 membrane expression. Downregulation of COMMD1 using silencing (si)RNA led to a transient loss of endogenous COMMD1 but did not affect activation of NKCC1 by hyperosmotic sucrose. Hyperosmolarity caused a transient increase in NKCC1 membrane expression, indicating regulated trafficking of NKCC1; downregulation of COMMD1 using siRNA reduced baseline (unstimulated) NKCC1 expression and blunted a transient elevation in NKCC1 membrane expression caused by hyperosmolarity. Constitutive downregulation of COMMD1 in HT29 engineered cells exhibited loss of COMMD1 and decreased NKCC1 membrane expression with no effect on activation of NKCC1. Loss of COMMD1 in Calu-3 cells and in HT29 cells led to reduced ubiquitinated NKCC1. The results indicate a role for COMMD1 in the regulation of NKCC1 membrane expression and ubiquitination.

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“…When Cu + is in excess, ATP7B sequesters Cu + within vesicles that traffic to the canalicular (apical) membrane (Braiterman et al, 2009;Forbes and Cox, 2000;Nyasae et al, 2014), where ATP7B facilitates the extrusion of excess Cu + into the bile (Fanni et al, 2005). Although a few proteins that affect trafficking of ATP7B have been identified, the molecular mechanisms responsible for polarized apical delivery of ATP7B remain poorly understood (Lim et al, 2006a,b;Materia et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Myosin Vb mediates Cu+ export in polarized hepatocytes

Gupta

Schell

Bhattacharjee

et al. 2016

Journal of Cell Science

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The cellular machinery responsible for Cu + -stimulated delivery of the Wilson-disease-associated protein ATP7B to the apical domain of hepatocytes is poorly understood. We demonstrate that myosin Vb regulates the Cu + -stimulated delivery of ATP7B to the apical domain of polarized hepatic cells, and that disruption of the ATP7B-myosin Vb interaction reduces the apical surface expression of ATP7B. Overexpression of the myosin Vb tail, which competes for binding of subapical cargos to myosin Vb bound to subapical actin, disrupted the surface expression of ATP7B, leading to reduced cellular Cu + export. The myosin-Vb-dependent targeting step occurred in parallel with hepatocyte-like polarity. If the myosin Vb tail was expressed acutely in cells just prior to the establishment of polarity, it appeared as part of an intracellular apical compartment, centered on γ-tubulin. ATP7B became selectively arrested in this compartment at high [Cu + ] in the presence of myosin Vb tail, suggesting that these compartments are precursors of donor-acceptor transfer stations for apically targeted cargos of myosin Vb. Our data suggest that reduced hepatic Cu + clearance in idiopathic non-Wilsonian types of disease might be associated with the loss of function of myosin Vb.

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Clusterin and COMMD1 Independently Regulate Degradation of the Mammalian Copper ATPases ATP7A and ATP7B

Cited by 79 publications

References 68 publications

Alzheimer’s disease due to loss of function: A new synthesis of the available data

Alzheimer’s disease due to loss of function: A new synthesis of the available data

COMMD1 interacts with the COOH terminus of NKCC1 in Calu-3 airway epithelial cells to modulate NKCC1 ubiquitination

Myosin Vb mediates Cu+ export in polarized hepatocytes

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