X-Nico

Colestipol

This leads to decreased enterohepatic recirculation of bile acids, increased synthesis of new bile acids by the liver from cholesterol, decreased liver cholesterol, increased LDL receptor expression, and decreasing LDL in blood.

DAB1

These findings established novel signaling functions for the LDL receptor gene family and suggested that VLDLR and APOER2 participate in transmitting the extracellular RELN signal to intracellular signaling processes initiated by DAB1.

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It docks to the intracellular part of the Reelin very low density lipoprotein receptor (VLDLR) and apoE receptor type 2 (ApoER2) and becomes tyrosine-phosphorylated following binding of Reelin to cortical neurons.

Endocytic cycle

LDL in the blood binds to LDL receptors on the surface of fibroblasts; these receptors concentrate in coated pits (they are about 200x as concentrated here as along the rest of the cell’s plasma membrane) and are internalised when the pit becomes a coated vesicle.

Endocytosis

The best-understood receptors that are found concentrated in coated vesicles of mammalian cells are the LDL receptor (which removes LDL from circulating blood), the transferrin receptor (which brings ferric ions bound by transferrin into the cell) and certain hormone receptors (such as that for EGF).

Evolocumab

PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood.

Lipoprotein

Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 on the LDL particle.

Low-density lipoprotein

To compensate for the decreased cholesterol availability, synthesis of hepatic LDL receptors is increased, resulting in an increased clearance of LDL particles from the blood.

Perlecan

Domain II comprises four repeats homologous to the ligand-binding portion of the LDL receptor with six conserved cysteine residues and a pentapeptide, DGSDE, which mediates ligand binding by the LDL receptor.

Receptor-mediated endocytosis

It is widely used for the specific uptake of certain substances required by the cell (examples include LDL via the LDL receptor or iron via transferrin).

SREBF1

This element is a decamer flanking the LDL receptor gene and other genes involved in, for instance, sterol biosynthesis.

Sterol regulatory element-binding protein

This releases the cytoplasmic portion of SREBP, which then travels to the nucleus where it activates transcription of target genes (e.g. LDL receptor gene)