Signaling through LRP1: Protection from atherosclerosis and beyond

Biochem Pharmacol. 2011 Jan 1;81(1):1-5. doi: 10.1016/j.bcp.2010.09.018. Epub 2010 Oct 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • Atherosclerosis / prevention & control*
  • Cell Differentiation
  • Endocytosis / physiology
  • Gene Expression Regulation / physiology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Receptors, LDL / metabolism*
  • Signal Transduction / physiology*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Lrp1 protein, mouse
  • Receptors, LDL
  • Tumor Suppressor Proteins

Grant support