LRP1

2022-06-29: reference:

LRP1 (LDL receptor-related protein 1) #

• The major Apolipoprotein E receptor. It interacts with a pile of proteins as a co-receptor, tagging along during their endocytosis.

  • With regards to ApoE, it stimulates cAMP influx.

• Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

  • Insulin treatment rapidly increases surface LRP1. LRP1 deficiency leads to impaired insulin signaling and reduced GLUT3/4 levels. Hyperglycemia suppresses expression, is decreased in Alzheimer’s and correlates with age at onset of disease.
    • The insulin-stimulated cell surface presentation of low density lipoprotein receptor-related protein in 3T3–L1 adipocytes is sensitive to phosphatidylinositide 3-kinase inhibition.
    • Insulin facilitates the hepatic clearance of plasma amyloid beta-peptide (1 40) by intracellular translocation of low-density lipoprotein receptor-related protein 1 (LRP-1) to the plasma membrane in hepatocytes
  • LRP1 is a major component of GLUT4-positive vesicles: Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling
    • Okay so I wonder how it decides what to colocalize with genetically. This is interesting.

• Implicated in clearance of Amyloid β out of the BBB.

• LRP1 is critical for the surface distribution and internalization of the NR2B NMDA receptor subtype

• LRP1-KO accelerates degradation of PSD-95 and GluR1: Low-density lipoprotein receptor-related protein 1 (LRP1) regulates the stability and function of GluA1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in neurons.

• Cell cholesterol modulates metalloproteinase-dependent shedding of low-density lipoprotein receptor-related protein-1 (LRP-1) and clearance function

  • ADAM12 and MT1-MMP. Release of the ectodomain was triggered by cholesterol depletion in epithelioid cells and impaired by cholesterol overload in fibroblastoid cells

• Inhibition of ADAM10 promotes the clearance of Aβ across the BBB by reducing LRP1 ectodomain shedding

  • Well this goes against being alpha secretase, now doesn’t it? I mean, I guess the other ADAM can take over.