Article

Ectodomains of the LDL Receptor-Related Proteins LRP1b and LRP4 Have Anchorage Independent Functions In Vivo

Leiden University Medical Center, Netherlands
PLoS ONE (Impact Factor: 3.23). 04/2010; 5(4):e9960. DOI: 10.1371/journal.pone.0009960
Source: PubMed

ABSTRACT

The low-density lipoprotein (LDL) receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL) receptor-related protein 1b (LRP1B) was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD) is fully viable with no apparent phenotype.

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    • "Finally, LRP1B gene encodes LDL receptor-related protein 1B and mediates cellular cholesterol uptake[54]. Dietrich et al.[55]reported that knockout of Lrp1b in mice results in early embryonic lethality. Association analysis identified LRP1B as a determinant of rat cholesterol concentrations in LDL, and a significant association with child body mass index (BMI) in human[56,57]. "
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    • "The absence of genetic association, however, does not preclude important roles for these multifunctional receptors in the molecular mechanisms that underlie the disease process. The very nature of their essential functions during the development of the embryo in general (Herz et al. 1992; Johnson et al. 2005; Dietrich et al. 2010; Karner et al. 2010), and the brain, in particular (Willnow et al. 1996; Trommsdorff "
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    • "In contrast to other LDL receptor family members [12], mice carrying a truncated form of LRP1b lacking the transmembrane region and therefore exclusively expressing a secreted extracellular domain appear phenotypically normal with normal plasma lipids [3]. Different from this finding, mice with more proximal truncations of the receptor are embryonically lethal, suggesting important functions of the extracellular part of LRP1b [13]. As stated above, LRP1b expression has been described in smooth muscle cells of the arterial wall. "
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