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Corrigendum Open Access | 10.1172/jci.insight.149528

The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance

Melinde Wijers, Paolo Zanoni, Nalan Liv, Dyonne Y. Vos, Michelle Y. Jäckstein, Marieke Smit, Sanne Wilbrink, Justina C. Wolters, Ydwine T. van der Veen, Nicolette Huijkman, Daphne Dekker, Niels Kloosterhuis, Theo H. van Dijk, Daniel D. Billadeau, Folkert Kuipers, Judith Klumperman, Arnold von Eckardstein, Jan Albert Kuivenhoven, and Bart van de Sluis

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Published April 8, 2021 - More info

Published in Volume 6, Issue 7 on April 8, 2021
JCI Insight. 2021;6(7):e149528. https://doi.org/10.1172/jci.insight.149528.
© 2021 LDL et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 8, 2021 - Version history
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Related article:

The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance
Melinde Wijers, … , Jan Albert Kuivenhoven, Bart van de Sluis
Melinde Wijers, … , Jan Albert Kuivenhoven, Bart van de Sluis
Receptor-mediated clearance of LDL and HDL cholesterol rely on Wiskott-Aldrich syndrome protein and SCAR homolog complex, an multiprotein complex of the endosomal protein sorting machinery.
Research Article Hepatology Metabolism

The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance

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Abstract

The evolutionary conserved Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is one of the crucial multiprotein complexes that facilitates endosomal recycling of transmembrane proteins. Defects in WASH components have been associated with inherited developmental and neurological disorders in humans. Here, we show that hepatic ablation of the WASH component Washc1 in chow-fed mice increases plasma concentrations of cholesterol in both LDLs and HDLs, without affecting hepatic cholesterol content, hepatic cholesterol synthesis, biliary cholesterol excretion, or hepatic bile acid metabolism. Elevated plasma LDL cholesterol was related to reduced hepatocytic surface levels of the LDL receptor (LDLR) and the LDLR-related protein LRP1. Hepatic WASH ablation also reduced the surface levels of scavenger receptor class B type I and, concomitantly, selective uptake of HDL cholesterol into the liver. Furthermore, we found that WASHC1 deficiency increases LDLR proteolysis by the inducible degrader of LDLR, but does not affect proprotein convertase subtilisin/kexin type 9–mediated LDLR degradation. Remarkably, however, loss of hepatic WASHC1 may sensitize LRP1 for proprotein convertase subtilisin/kexin type 9–induced degradation. Altogether, these findings identify the WASH complex as a regulator of LDL as well as HDL metabolism and provide in vivo evidence for endosomal trafficking of scavenger receptor class B type I in hepatocytes.

Authors

Melinde Wijers, Paolo Zanoni, Nalan Liv, Dyonne Y. Vos, Michelle Y. Jäckstein, Marieke Smit, Sanne Wilbrink, Justina C. Wolters, Ydwine T. van der Veen, Nicolette Huijkman, Daphne Dekker, Niels Kloosterhuis, Theo H. van Dijk, Daniel D. Billadeau, Folkert Kuipers, Judith Klumperman, Arnold von Eckardstein, Jan Albert Kuivenhoven, Bart van de Sluis

×

Original citation: JCI Insight. 2019;4(11):e126462. https://doi.org/10.1172/jci.insight.126462

Citation for this corrigendum: JCI Insight. 2021;6(7):e149528. https://doi.org/10.1172/jci.insight.149528

Following the publication of this article, a reader noted that Figure 4C contained a Western blot that was published in a Circulation Research publication by the same group (1). The authors have indicated that the errors in Figure 4C occurred during figure preparation. The correct panel is below.

Figure 4C

The authors regret the error.

1. Fedoseienko A, et al. The COMMD family regulates plasma LDL levels and attenuates atherosclerosis through stabilizing the CCC complex in endosomal LDLR trafficking. Circ Res. 2018;122(12):1648–1660.

Footnotes

See the related article at The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance.

Version history
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