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Journal of Lipid Research, Vol. 50, S287-S292, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Receptors

Expanding functions of lipoprotein receptors

Joachim Herz¹, Ying Chen, Irene Masiulis and Li Zhou

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

We acknowledge support from the National Institutes of Health, the Alexander-von-Humboldt Foundation, the American Heart Association, and the University of Texas Southwestern Medical Center.

Published, JLR Papers in Press, November 17, 2008.

¹ To whom correspondence should be addressed. e-mail: joachim.herz{at}utsouthwestern.edu

ABSTRACT

Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types. Beginning with the appearance of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors evolved. Originally, these cell surface proteins were thought to merely mediate the traffic of lipids and nutrients between cells and, in some cases, by functioning as scavenger receptors, remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular space and the cell surface. Over the last decade, this picture has fundamentally changed. We now appreciate that many of these receptors are not mere cargo transporters; they are deeply embedded in the machinery by which cells communicate with each other. By physically interacting and coevolving with fundamental signaling pathways, lipoprotein receptors have occupied essential and surprisingly diverse functions that are indispensable for integrating the complex web of cellular signal input during development and in differentiated tissues.

Supplementary key words nervous system • Apoer2 • Vldlr • LRP1 • LRP4

Abbreviations: Vldlr, very low-density lipoprotein receptor; Apoer2, apolipoprotein E receptor 2; EGF, epidermal growth factor; PI3K, phosphatidylinositol 3-kinase; PKB/Akt, protein kinase B; GSK3β, glycogen synthase kinase-3β; CrkL, Crk-like; CREB, cAMP-response element binding protein; LRP, LDL receptor-related protein; Dab1, Disabled-1; ICD, intracellular domain; JIP, cJun-N-terminal kinase interacting protein; NMDA, N-methyl-D-aspartic acid; NMDAR, NMDA receptor; PSD, postsynaptic density protein 95; SFK, Src family tyrosine kinase; TSP, thrombospondin; APP, amyloid precursor protein; ApoE, apolipoprotein E; APLP2, amyloid precursor-like protein 2; MUSK, muscle-specific kinase; AchR, acetylcholine receptor

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