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LDL Receptor–Related Protein-1

Gonias, Steven L., Campana, W. Marie·2014·The American Journal of Pathology
DOI 10.1016/j.ajpath.2013.08.029
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Figure 1 Molecular models showing the organization of structural domains in LRP1 and the docking of a representative ligand to complement-like repeats in LRP1. A : The depicted domains in LRP1 are common to the LDL receptor family. Stars are present in the intracellular region of LRP1 to represent motifs that function as endocytosis signals and/or as docking sites for cell-signaling proteins including NPXY, YxxL, and dileucine. B : A representative LRP1 ligand, the 18-kDa receptorbinding domain of a 2-macroglobulin, which is a free-standing domain in the activated state of the protein, is shown in pink. Two lysine residues in a single a -helix, highlighted in blue, are essential for binding to LRP1. These lysine residues interact with acidic amino acids in the LRP1 complementlike repeats. The fourth and fi fth complement-like repeats in CCR2 are shown in orange, and the acidic amino acids in these domains are highlighted in black. The approximate positions of calcium are shown. EGF, epidermal growth factor.
Figure 1 Molecular models showing the organization of structural domains in LRP1 and the docking of a representative ligand to complement-like repeats in LRP1. A : The depicted domains in LRP1 are common to the LDL receptor family. Stars are present in the intracellular region of LRP1 to represent motifs that function as endocytosis signals and/or as docking sites for cell-signaling proteins including NPXY, YxxL, and dileucine. B : A representative LRP1 ligand, the 18-kDa receptorbinding domain of a 2-macroglobulin, which is a free-standing domain in the activated state of the protein, is shown in pink. Two lysine residues in a single a -helix, highlighted in blue, are essential for binding to LRP1. These lysine residues interact with acidic amino acids in the LRP1 complementlike repeats. The fourth and fi fth complement-like repeats in CCR2 are shown in orange, and the acidic amino acids in these domains are highlighted in black. The approximate positions of calcium are shown. EGF, epidermal growth factor.CC-BY-NC-ND · From the PDF
Figure 2 LRP1 interaction map generated using the Ingenuity IPA System. The map was limited to interactions involving the nervous system in infl ammatory disease and in the in fl ammatory response. Interactions are strati fi ed in relation to the location of the LRP1-interacting gene product relative to the cell. Interacting gene products include cytokines ( closed square ), growth factors ( broken square ), proteases ( horizontally elongated diamond ), other enzymes ( vertically elongated diamond ), proteins involved in transport ( trapezoid ), transmembrane receptors ( vertically elongated oval ), ion channel subunits ( broken vertically elongated rectangle ), kinases ( inverted triangle ), transcription regulators ( horizontally elongated oval ), and phosphatases ( triangle ). Other categories of gene products are shown as circles . Direct interactions are shown with a solid line and indirect interactions with a broken line. A solid line without an arrow implies a binding interaction. An arrowhead at the end of a broken line implies that one gene product acts on the other. A perpendicular bar implies an inhibitory interaction.
Figure 2 LRP1 interaction map generated using the Ingenuity IPA System. The map was limited to interactions involving the nervous system in infl ammatory disease and in the in fl ammatory response. Interactions are strati fi ed in relation to the location of the LRP1-interacting gene product relative to the cell. Interacting gene products include cytokines ( closed square ), growth factors ( broken square ), proteases ( horizontally elongated diamond ), other enzymes ( vertically elongated diamond ), proteins involved in transport ( trapezoid ), transmembrane receptors ( vertically elongated oval ), ion channel subunits ( broken vertically elongated rectangle ), kinases ( inverted triangle ), transcription regulators ( horizontally elongated oval ), and phosphatases ( triangle ). Other categories of gene products are shown as circles . Direct interactions are shown with a solid line and indirect interactions with a broken line. A solid line without an arrow implies a binding interaction. An arrowhead at the end of a broken line implies that one gene product acts on the other. A perpendicular bar implies an inhibitory interaction.CC-BY-NC-ND · From the PDF
Figure 3 IHC analysis to detect LRP1 in the nervous system. A : LRP1 immunostaining of mouse cerebral cortex. LRP1 was detected with a primary polyclonal antibody that detects the b -chain (Sigma-Aldrich, St. Louis, MO). Staining was conducted using a Ventana System (Tucson, AZ). B : A section of rat sciatic nerve distal to a crush injury site, which was recovered 3 days after nerve injury. LRP1 was detected using polyclonal antibody R2629. The section is counterstained with methylene green. Representative LRP1-immunopositive Schwann cells are marked with arrows . The asterisk marks a macrophage. Scale bars: 35 m m ( A ); 12 m m ( B ).
Figure 3 IHC analysis to detect LRP1 in the nervous system. A : LRP1 immunostaining of mouse cerebral cortex. LRP1 was detected with a primary polyclonal antibody that detects the b -chain (Sigma-Aldrich, St. Louis, MO). Staining was conducted using a Ventana System (Tucson, AZ). B : A section of rat sciatic nerve distal to a crush injury site, which was recovered 3 days after nerve injury. LRP1 was detected using polyclonal antibody R2629. The section is counterstained with methylene green. Representative LRP1-immunopositive Schwann cells are marked with arrows . The asterisk marks a macrophage. Scale bars: 35 m m ( A ); 12 m m ( B ).CC-BY-NC-ND · From the PDF

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Metadata

Authors
Gonias, S. L., & Campana, W. M.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2014-01
Volume
184
Issue
1
Pages
18-27
ISSN
0002-9440
DOI
10.1016/j.ajpath.2013.08.029
Cited by
175
References
3
Language
en
Licence
Funders
National Institutes of Health (R01 NS057456, R01 NS054671, R01 HL060551)

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