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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Lipoprotein receptors – an evolutionarily ancient multifunctional receptor family

Marco Dieckmann1, 2 / Martin Frederik Dietrich1 / Joachim Herz1

1Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9046, USA

2Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, D-55099 Mainz, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 391, Issue 11, Pages 1341–1363, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/bc.2010.129, September 2010

Publication History:
Received:
2010-05-04
Accepted:
2010-07-30
Published Online:
2010-09-24

Abstract

The evolutionarily ancient low-density lipoprotein (LDL) receptor gene family represents a class of widely expressed cell surface receptors. Since the dawn of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors have evolved. In accordance with the now obsolete ‘one-gene-one-function’ hypothesis, these cell surface receptors were orginally perceived as mere transporters of lipoproteins, lipids, and nutrients or as scavenger receptors, which remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular environment and the cell surface. This picture has since undergone a fundamental change. Experimental evidence has replaced the perception that these receptors serve merely as cargo transporters. Instead it is now clear that the transport of macromolecules is inseparably intertwined with the molecular machinery by which cells communicate with each other. Lipoprotein receptors are essentially sensors of the extracellular environment that participate in a wide range of physiological processes by physically interacting and coevolving with primary signal transducers as co-regulators. Furthermore, lipoprotein receptors modulate cellular trafficking and localization of the amyloid precursor protein (APP) and the β-amyloid peptide (Aβ), suggesting a role in the pathogenesis of Alzheimer's disease. Moreover, compelling evidence shows that LDL receptor family members are involved in tumor development and progression.

Keywords: Alzheimer; ApoE; atherosclerosis; brain development; LRP; neuromuscular junction

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