Search results for VLDLR

Showing 13 results out of 17

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (3 results from a total of 3)

Identifier: R-HSA-5216079
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: VLDLR: P98155
Identifier: R-HSA-8855141
Species: Homo sapiens
Compartment: lysosomal membrane
Primary external reference: UniProt: VLDLR: P98155
Identifier: R-HSA-8855136
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: VLDLR: P98155

Reaction (7 results from a total of 11)

Identifier: R-HSA-8855111
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of plasma cholesterol homeostasis by binding to low-density lipid receptor family members and promoting their degradation in lysosomes (Poirier et al. 2008). In mice, it was observed that circulating PCSK9 can regulate VLDLR protein levels in adipose tissue and thereby, fat accumulation. The absence of PCSK9 led to an increase in lipid uptake resulting in adipocyte hypertrophy which was LDLR-independent (Roubtsova et al. 2011). Whether increased fat deposition also occurs in humans lacking functional PCSK9 remains to be elucidated.
Identifier: R-HSA-8854462
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Very low-density lipoproteins (VLDLs) are produced in the liver to transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters in the hydrophilic environment of the bloodstream. They comprise triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). Of the protein content, two other apolipoproteins are constituents; apolipoprotein C-I (APOC around 20%) (Westerterp et al. 2007) and apolipoprotein C4 (APOC4, minor amount) (Kotite et al. 2003). After release from the liver, circulating VLDL particles can bind very low-density lipoprotein receptors (VLDLR) (Sakai et al. 1994) on extra-hepatic target cells and undergo endocytosis (Go & Mani 2012). VLDL uptake by VLDLR represents a minor contribution towards VLDL metabolism. The majority of VLDL is catalysed by lipoprotein lipase (LPL) which hydrolyses TAGs from VLDL, converting it to intermediate-density lipoprotein (IDL). IDL can be further hydrolysed by hepatic lipase to cholesterol-rich low-density lipoprotein (LDL).

VLDLR consists of five functional domains that resemble the LDL receptor. It is highly expressed in tissues that actively metabolise fatty acids as a source of energy. Binding of VLDLs to VLDLR appears to be inhibited by apolipoprotein C-I (APOC1), therby slowing the clearance of triglyceride-rich lipoproteins from the circulation (Westerterp et al. 2007). The APOE/C1/C4/C2 gene cluster is closely associated with plasma lipid levels, atherosclerotic plaque formation, and thereby implicated in the development of coronary artery disease and Alzheimer’s disease (Xu et al. 2015).
Identifier: R-HSA-8854466
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Reelin (RELN) (DeSilva et al. 1997) is an extracellular matrix serine protease highly expressed in the brain that plays a role in neural cell positioning during brain development by regulating their microtubule function and neuronal migration. It can bind to the extracellular domains of lipoprotein receptors VLDLR and APOER2 to induce tyrosine phosphorylation of disabled-1 (DAB1), an adaptor protein bound to the cytoplasmic tails of these receptors that is a phosphorylation target for a signaling cascade trigggered by RELN. This suggests VLDLR and APOER2 participate in transmitting the extracellular RELN signal to intracellular signaling processes initiated by DAB1 (Hiesberger et al. 1999). In post-mortem studies of schizophrenia sufferers, RELN was found to be significantly reduced (by up to 50%) in brain samples whereas DAB1 was observed to be at normal levels, suggesting a role for RELN in schizophrenia (Impagnatiello et al. 1998).
Identifier: R-HSA-8854628
Species: Homo sapiens
Compartment: plasma membrane, cytosol
The E3 ubiquitin-protein ligase (MYLIP, aka IDOL) mediates the lysine-63 polyubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8 (Sorrentino et al. 2011). It acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating degradation of LDLR (Hong et al. 2010). Despite some similarities, the MYLIP and PCSK9 ubiquitination pathways for controlling (V)LDLR abundance appear to be independent of each other. MYLIP is a transcriptional target of liver X receptors (NR1H2 and NR1H3), which can increase MYLIP expression and hence decerease (V)LDLR levels (Zelcer et al. 2009, Hong et al. 2010, Sorrentino & Zelcer 2010, Zhang et al. 2012).
Identifier: R-HSA-8855131
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Once proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to very low-density lipoprotein receptor (VLDLR), the resultant complex is internalised via the canonical clathrin-dependent endocytic machinery. This degradation route that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve proteasomal or autophagy pahtways (Zhang et al. 2007, Poirier et al. 2008).
Identifier: R-HSA-8855259
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
SH3 domain-containing kinase-binding protein 1 (SH3KBP1, aka CIN85) is an adapter protein involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases (Fuchigami et al. 2013).
Identifier: R-HSA-8855130
Species: Homo sapiens
Compartment: plasma membrane, lysosomal membrane
Once proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to very low-density lipoprotein receptor (VLDLR), the resultant complex is internalised via the canonical clathrin-dependent endocytic machinery. This degradation route that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve proteasomal or autophagy pathways. The PCSK9:VLDLR:Clathrin-coated vesicle complex translocates from the plasma membrane, via endosomes to the lysosomal membrane where the receptor is degraded (Zhang et al. 2007, Poirier et al. 2008).

Pathway (2 results from a total of 2)

Identifier: R-HSA-8866427
Species: Homo sapiens
The steps involved in proprotein convertase PCSK9-induced degradation of VLDLR are described here (Poirier et al. 2008). The rate of this catabolic process plays a clinically significant role in determining the efficiency of lipoprotein clearance from the blood.
Identifier: R-HSA-8964043
Species: Homo sapiens
Circulating chylomicrons acquire molecules of apolipoproteins C and E and through interaction with endothelial lipases lose a large fraction of their triacylglycerol. These changes convert them to chylomicron remnants which bind to LDL receptors, primarily on the surfaces of liver cells, clearing them from the circulation (Redgrave 2004).
Most very-low-density lipoproteins (VLDL) are converted to low-density lipoproteins (LDL) (VLDL remodeling pathway). A small fraction are taken up by VLDL receptors on extrahepatic cells, as annotated here. Clearance of LDL from the blood involves binding to LDL receptors associated with coated pits at the cell surface, forming complexes that are internalized and passed via clathrin-coated vesicles to endosomes, where they dissociate. The LDL particles move into lysosomes and are degraded while the LDL receptors are returned to the cell surface. This process occurs in most cell types but is especially prominent in hepatocytes. It plays a major role in returning cholesterol from peripheral tissues to the liver (Hobbs et al. 1990).
Clearance of circulating HDL particles involves particle binding to cell-surface SR-BI receptors, particle disassembly with rlease of pre-beta HDL (Silver & Tall 2001), and uptake of the latter mediated by cell-surface CUBN:AMN complex (Kozyraki et al. 1999).
VLDLR internalization plays a clinically significant role in determining the efficiency of lipoprotein clearance from the blood (Poirier et al. 2008).

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Steve Jupe
Designer: Cristoffer Sevilla
VLDLR icon
Very low-density lipoprotein receptor
Cite Us!