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LR11, an LDL Receptor Gene Family Member, Is a Novel Regulator of Smooth Muscle Cell Migration

LR11, an LDL Receptor Gene Family Member, Is a Novel Regulator of Smooth Muscle Cell Migration,Yanjuan Zhu,Hideaki Bujo,Hiroyuki Yamazaki,Kenji Ohwaki

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LR11, an LDL Receptor Gene Family Member, Is a Novel Regulator of Smooth Muscle Cell Migration   (Citations: 12)
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LR11, a member of the LDL receptor family, is highly expressed in vascular smooth muscle cells (SMCs) of the hyperplastic intima, and induces enhanced migration of SMCs in vitro via its upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. In this study, we have delineated the mechanism by which LR11 elevates the expression levels of uPAR in SMCs. Secretion of soluble LR11 is induced in SMCs during the rapidly proliferating phase, and the secreted LR11 induces the migration activities of SMCs. Both the cell-anchored and secreted forms of LR11 have the capacity to bind to and form complexes with uPAR. LR11-overexpressing cells show significantly enhanced uPAR binding, but decreased uPAR internalization. LR11 colocalizes with uPAR on the cell surface and inhibits the LDL receptor-related protein (LRP)-mediated binding and internalization of uPAR. Thus, LR11 mediates the uPAR localization to the plasma membrane. LR11 is highly expressed in the atheromatous plaque areas of apoE knockout mice, particularly in the intimal SMCs at the border between intima and media. The neutralization of LR11 function with anti-LR11 antibody reduced cuff-induced intimal thickness in mice. The novel mechanism of regulation of uPAR localization in SMCs accompanied with enhanced migration activity possibly constitutes an important factor in the process of atherosclerosis and arterial remodeling. (Circ Res. 2004;94:752-758.)
Published in 2010.
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    Takeshi Ikeuchi, et al. Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Patients wi...

    • ...The function of soluble receptors, for instance as carrier proteins, is virtually undescribed but, like LRP, the full-length receptors are capable of uptake and endocytosis of bound ligands and facilitate signal transduction in response to ligand binding (10, 39)...
    • ...AP-2 -chain of brain extracts was efficiently precipitated by a SorLA-cd GST fusion protein but not by a truncated SorLA-cd not containing the AC [(30-54)], by GST alone, or by the cd of SorCS1c, another member of the Vps10p-D receptor family (Fig. 4A, upper panel)...
    • ...Precipitation was performed with GST or GST-fusion proteins containing the cd of SorLA wt or (30-54) or of SorCS1c...
    • ...In agreement with these findings, the wt SorLAcd, but not the truncated construct (30-54), was found to mediate the pull-down of AP-1 from brain lysates (Fig. 7C)...
    • ...Precipitations were performed with GST or GST-fusion proteins containing the cd of SorLA [wt or (30- 54)] or of SorCS1c and analyzed by Western blotting and anti-AP-1 -chain immunoglobulin...

    Morten S. Nielsen, et al. Sorting by the Cytoplasmic Domain of the Amyloid Precursor Protein Bin...

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