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Cited by 122Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

Signaling through LRP1: Protection from atherosclerosis and beyond

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Boucher, Philippe, Herz, Joachim·2011·Biochemical Pharmacology
DOI 10.1016/j.bcp.2010.09.018PMC PMC2991482
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Abstract

The low-density lipoprotein receptor-related protein (LRP1) is a multifunctional cell surface receptor that belongs to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 consists of an 85-kDa membrane-bound carboxyl fragment (β chain) and a non-covalently attached 515-kDa (α chain) amino-terminal fragment. Through its extracellular domain, LRP1 binds at least 40 different ligands ranging from lipoprotein and protease inhibitor complex to growth factors and extracellular matrix proteins. LRP-1 has also been shown to interact with scaffolding and signaling proteins via its intracellular domain in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. LRP-1 is thus implicated in two major physiological processes: endocytosis and regulation of signaling pathways, which are both involved in diverse biological roles including lipid metabolism, cell growth/differentiation processes, degradation of proteases, and tissue invasion. The embryonic lethal phenotype obtained after target disruption of the LRP-1 gene in the mouse highlights the biological importance of this receptor and revealed a critical, but yet undefined role in development. Tissue-specific gene deletion studies also reveal an important contribution of LRP1 in vascular remodeling, foam cell biology, the central nervous system, and in the molecular mechanisms of atherosclerosis.

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References 54 · Cited by 122

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Authors
Boucher, P., & Herz, J.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Boucher, Philippe
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2011-01
Volume
81
Issue
1
Pages
1-5
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2010.09.018
PMC
PMC2991482
OpenAlex
W1968238953
Cited by
122
References
54
Citations by year
2026: 7 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 8
FWCI
4.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • American Health Assistance Foundation
  • Agence Nationale de la Recherche (ANR-06-PHYSIO-032-01, ANR-09-BLAN-0121-01)
  • Université de Strasbourg
  • Fondation de France
  • Centre National pour la Recherche Scientifique et Technique
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
LRP1, low density lipoprotein receptor-related protein, atherosclerosis, LDL receptor family, receptor signaling, endocytosis, ligand binding, protease-inhibitor complex, foam cells, vascular remodeling, embryonic lethality, tissue-specific gene deletion, lipid metabolism, protease degradation, central nervous system
MeSH terms
Animals, Cell Differentiation, Endocytosis, Gene Expression Regulation, Macrophages, Protein Binding, Receptors, LDL, Signal Transduction, Mice, Knockout, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Atherosclerosis, Mice

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