Function VLDL receptor

1 function

1.1 beyond nervous system

1.1.1 lipoprotein uptake

1.1.1.1 endocytosis




1.2 in nervous system

1.2.1 neuronal migration

function
beyond nervous system

vldlr peripheral lipoprotein receptor functions in lipoprotein metabolism, cardiac fatty acid metabolism, , fat deposition. in effect, vldlr allow cholesterol reach tissues bloodstream, may used in cellular membranes. in addition, allow fatty acids cells may used energy source. overall, vldlr modulates extra-hepatic metabolism of triglyceride-rich lipoproteins.

lipoprotein uptake

vldlr plays discrete role in lipid metabolism, more significant in stressed situations. mice double knockouts in vldlr , ldlr have higher serum triglyceride levels knockout in ldlr gene. in addition, ldlr knockout mice overexpressing vldlr have decreased serum triglyceride levels. although fat deposition close normal without vldlr, role gains importance when ldlr deficient. despite knowledge on role in lipoprotein uptake, complete mechanism of lipid metabolism performed vldlr not understood.

endocytosis

vldlr known employ endocytosis, although exact mechanism of process unknown protein. endocytosis mediated through npxy sequences known signal receptor internalization through clathrin-coated pits. presence of sequence in cytoplasmic tail of vldlr makes endocytosis possible. in general, lipoprotein receptors undergo process endocytosed ligand clathrin-coated pits. here, transported , late endosomes until reaching lysosome. @ point, hydrolysis occurs , lipoprotein released cytoplasm while receptors recycled cell surface. not yet confirmed if vldlr follows exact mechanism, 1 closely related likely.

in nervous system

the reelin pathway, representing vldlr’s role in process.

in addition role throughout body, vldlr has unique role in brain. key component of reelin pathway, functions in neuronal migration. vldlr links reelin protein intracellular signaling protein, dab1, tells individual neurons go within anatomy of brain. mutations in vldlr not lead major disorganization seen in reelin mutations. however, vldlr mutation lead disorganization located in cerebellum, vldlr believed prominent.

neuronal migration

vldlr expressed on migrating neurons guide them proper location in brain. process part of reelin pathway, responsible inside-out formation of six-layered neocortex. despite discovery of pathway, many of specifics , molecular mechanisms of process still being debated. presence of 2 reelin receptors, vldlr , apoer2, has made difficult distinguish each protein’s specific function.

organization of 6 layered neocortex. in absence of vldlr, neuroblasts of cortical plate invade marginal zone above.

vldlr responsible correct layering of pyramidal cells layer 1 of cerebral cortex. in particular, absence of vldlr may lead ectopic accumulation of pyramidal cells in region. vldlr not affect migration of born cells organized layer, since absence results in invasion of these neuroblasts marginal zone, theorized vldlr may encode “stop signal.” supported fact vldlr expressed in cortical plate adjacent reelin-expressing cells, cajal–retzius cells, , in intermediate zone. however, definitive evidence has not yet been found. in general, reelin binds vldlr , undergoes endocytosis via clathrin-coated vesicles. meanwhile, intracellular protein, dab1, has pi/ptb domain interacts npxy sequence found in cytoplasmic tail of vldlr. result, dab1 tyrosine phosphorylated , reelin degraded. finally, phosphorylated dab1 activates intracellular signaling cascade directs neuroblasts proper location through alteration of cytoskeleton. many of specifics of pathway still being investigated. not yet known if dab1 phosphorylated result of endocytosis of reelin, or if there mechanism @ play. in addition organization of neocortex, vldlr plays role in neuronal migration of hippocampus , purkinje cells of cerebellum. yet, information on process still unknown.