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PMID:10085125

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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

Significance

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


See also

References

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