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Disrupted recycling of the low density lipoprotein receptor by PCSK9 is not mediated by residues of the cytoplasmic domain

Strøm, Thea Bismo, Holla, Øystein L., Tveten, Kristian, Cameron, Jamie, Berge, Knut Erik, Leren, Trond P.·2010·Molecular Genetics and Metabolism
DOI 10.1016/j.ymgme.2010.05.003
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Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-translationally regulates the number of cell-surface low density lipoprotein receptors (LDLR). This is accomplished by the ability of PCSK9 to mediate degradation of the LDLR. The underlying mechanism involves binding of secreted PCSK9 to the epidermal growth factor-like repeat A of the extracellular domain of the LDLR at the cell surface, followed by lysosomal degradation of the internalized LDLR:PCSK9 complex. However, the mechanism by which the normal recycling of the LDLR is disrupted by PCSK9, remains to be determined. In this study we have investigated the role of the cytoplasmic domain of the LDLR for this process. This has been done by studying the ability of a mutant LDLR (K811X-LDLR) which lacks the cytoplasmic domain, to be degraded by PCSK9. We show that this mutant receptor is degraded by PCSK9. Thus, the machinery which directs the LDLR:PCSK9 complex to the lysosomes for degradation, does not interact with the cytoplasmic domain of the LDLR.

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  • LDLR proteins lacking the cytoplasmic domain still undergo PCSK9-mediated degradation, suggesting that modifications of the cytoplasmic domain or interactions with ubiquitin or adaptor proteins are not involved in routing LDLR:PCSK9 complexes for intracellular degradation.

    “LDLR proteins lacking the cytoplasmic domain125 still undergo PCSK9-mediated degradation, suggesting that modifications of the cytoplasmic domain or interactions with ubiquitin or adaptor proteins are not involved in routing LDLR:PCSK9 complexes for intracellular degradation.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [125]

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Research works printed but not linked: 24

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Metadata

Authors
Strøm, T. B., Holla, Ø. L., Tveten, K., Cameron, J., Berge, K. E., & Leren, T. P.
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2010-09
Volume
101
Issue
1
Pages
76-80
ISSN
1096-7192
DOI
10.1016/j.ymgme.2010.05.003
Cited by
32
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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