PMID:10085125

Citation	Nielsen, MS, Jacobsen, C, Olivecrona, G, Gliemann, J and Petersen, CM (1999) Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J. Biol. Chem. 274:8832-6
Abstract	Lipoprotein lipase and the receptor-associated protein (RAP) bind to overlapping sites on the low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP). We have investigated if lipoprotein lipase interacts with the RAP binding but structurally distinct receptor sortilin/neurotensin receptor-3. We show, by chemical cross-linking and surface plasmon resonance analysis, that soluble sortilin binds lipoprotein lipase with an affinity similar to that of LRP. The binding was inhibited by heparin and RAP and by the newly discovered sortilin ligand neurotensin. In 35S-labeled 3T3-L1 adipocytes treated with the cross-linker dithiobis(succinimidyl propionate), lipoprotein lipase-containing complexes were isolated by anti-sortilin antibodies. To elucidate function in cells, sortilin-negative Chinese hamster ovary cells were transfected with full-length sortilin and shown to express about 8% of the receptors on the cell surface. These cells degraded 125I-labeled lipoprotein lipase much faster than the wild-type cells. The degradation was inhibited by unlabeled lipoprotein lipase, indicating a saturable pathway, and by RAP and heparin. Moreover, inhibition by the weak base chloroquine suggested that degradation occurs in an acidic vesicle compartment. The results demonstrate that sortilin is a multifunctional receptor that binds lipoprotein lipase and, when expressed on the cell surface, mediates its endocytosis and degradation.
Links	PubMed
Keywords	Adaptor Proteins, Vesicular Transport; Adipocytes/metabolism; Animals; Biosensing Techniques; CHO Cells; Chloroquine/pharmacology; Cricetinae; Cross-Linking Reagents; Endocytosis; Heparin/pharmacology; Lipoprotein Lipase/metabolism; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurotensin/pharmacology; Protein Binding; Succinimides; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BOVIN:LIPL	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q99523	F		Seeded From UniProt	complete
HUMAN:AMRP	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q99523	F		Seeded From UniProt	complete
HUMAN:SORT	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P11151	F		Seeded From UniProt	complete
HUMAN:SORT	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P30533	F		Seeded From UniProt	complete
HUMAN:SORT	located_in	GO:0009986: cell surface	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SORT	involved_in	GO:0051005: negative regulation of lipoprotein lipase activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SORT	enables	GO:0019899: enzyme binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P06858	F		Seeded From UniProt	complete
HUMAN:LIPL	enables	GO:0005102: signaling receptor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q99523	F		Seeded From UniProt	complete

References

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