Signaling through LRP1: Protection from atherosclerosis and beyond

Philippe Boucher, Joachim Herz

Research output: Contribution to journalComment/debate

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalBiochemical Pharmacology
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • Atherosclerosis
  • Cell signaling
  • LRP1
  • Lipid metabolism
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint Dive into the research topics of 'Signaling through LRP1: Protection from atherosclerosis and beyond'. Together they form a unique fingerprint.

  • Cite this