May P, Woldt E, Matz RL, Boucher P.. The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions. Ann Med 39: 219-228

Universität Freiburg, Medizinische Klinik II/Zentrum für Neurowissenschaften, Freiburg, Germany.
Annals of Medicine (Impact Factor: 3.89). 02/2007; 39(3):219-28. DOI: 10.1080/07853890701214881
Source: PubMed


The low-density lipoprotein (LDL) receptor is the founding member of a family of seven structurally closely related transmembrane proteins (LRP1, LRP1b, megalin/LRP2, LDL receptor, very low-density lipoprotein receptor, MEGF7/LRP4, LRP8/apolipoprotein E receptor2). These proteins participate in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins. While currently available data suggest that the role of the LDL receptor is limited to the regulation of cholesterol homeostasis by receptor-mediated endocytosis of lipoprotein particles, there is growing experimental evidence that the other members of the gene family have additional physiological functions as signal transducers. In this review, we focus on the latest discovered functions of two major members of this family, LRP1 and megalin/LRP2, and on the newly elucidated physiological role of a third member of the family, MEGF7/LRP4, which can also function as a modulator of diverse signaling pathways during development.

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    • "Responsible membrane proteins in the Wnt signaling pathway, however, are not fully elucidated in chondrocyte differentiation. The low-density lipoprotein receptor (LDLR)-related protein 4 (LRP4) is a transmembrane protein and a member of the LDLR family [4]. In osteoblasts, LRP4 is a receptor for Wnt signaling inhibitors of Dkk1, Sost, and Sostdc1 (Wise), and reduces Wnt/bcatenin signaling during bone development [5] [6]. "
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    • "LDLa is a cysteine-rich repeat domain that plays a central role in metabolism of mammalian cholesterol, especially during the receptor protein binds LDL [67]. It enters the cell by endocytosis [68]. Successive cysteine-rich repeats of ~ 40 residues are located at the amino-terminus of this multi-domain membrane protein. "
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    • "Of the 4 putative targets of miR-143 which have been reported previously to be up-regulated in SNEB, LRP2 is involved in lipid metabolism and is of particular interest because the metabolism of lipids is altered during SNEB [51,52]. LRP2 is implicated in lipid metabolism through its role as a receptor for sterols, steroid hormones bound to carrier proteins [53] like lipoproteins [54] and apolipoprotein M of liver [55-57]. A study of miRNA based modulation of obesity also reported LRP2 as a putative target of miR-130a, with roles in lipid metabolism [58]. "
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