| Characterization of the VPS10 domain of SorLA/LR11 as binding site for the neuropeptide HA. | |
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MedLine Citation:
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PMID: 12530537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The single transmembrane receptor sorLA/LR11 contains binding domains typical for the low-density lipoprotein receptors and a VPS10 domain which, in the related receptor sortilin, binds the neuropeptide neurotensin. SorLA is synthesized as a proreceptor which is processed to the mature form by a furin-like propeptidase. Endogenous sorLA and its hydra homologue HAB bind the neuropeptide head activator (HA). Transiently expressed partial sorLA constructs were investigated for ligand binding. We found that HA binds with nanomolar affinity to the VPS10 domain. The sorLA propeptide also bound to the VPS10 domain, whereas the receptor-associated protein RAP interacted both with the class A repeats and the VPS10 domain. The sorLA propeptide inhibited binding of HA to full-length sorLA and to the VPS10 domain. It also interfered with binding of HA to hydra HAB, which is taken as evidence for a highly conserved tertiary structure of the VPS10 domains of this receptor in hydra and mammals. The propeptide inhibited HA-stimulated mitosis and proliferation in the human neuroendocrine cell line BON and the neuronal precursor cell line NT2. We conclude that sorLA is necessary for HA signaling and function. |
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Authors:
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Julia Lintzel; Inga Franke; I Björn Riedel; H Chica Schaller; Wolfgang Hampe |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biological chemistry Volume: 383 ISSN: 1431-6730 ISO Abbreviation: Biol. Chem. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2003-01-17 Completed Date: 2003-06-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9700112 Medline TA: Biol Chem Country: Germany |
Other Details:
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Languages: eng Pagination: 1727-33 Citation Subset: IM |
Affiliation:
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Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistr. 52, D-20246 Hamburg, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Binding Sites Blotting, Western CHO Cells COS Cells Cell Division / physiology Cells, Cultured Cercopithecus aethiops Cricetinae Humans Immunohistochemistry LDL-Receptor Related Proteins Membrane Transport Proteins* Mitosis / physiology Neuropeptides / genetics, metabolism* Protein Structure, Tertiary Pyrrolidonecarboxylic Acid / analogs & derivatives Receptors, LDL / genetics, metabolism* Signal Transduction / physiology Transfection |
| Chemical | |
Reg. No./Substance:
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0/LDL-Receptor Related Proteins; 0/Membrane Transport Proteins; 0/Neuropeptides; 0/Receptors, LDL; 0/SORL1 protein, human; 79943-68-3/head activator peptide; 98-79-3/Pyrrolidonecarboxylic Acid |
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