Document Detail


Characterization of the VPS10 domain of SorLA/LR11 as binding site for the neuropeptide HA.
MedLine Citation:
PMID:  12530537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Julia Lintzel; Inga Franke; I Björn Riedel; H Chica Schaller; Wolfgang Hampe
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological chemistry     Volume:  383     ISSN:  1431-6730     ISO Abbreviation:  Biol. Chem.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2003-01-17     Completed Date:  2003-06-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1727-33     Citation Subset:  IM    
Affiliation:
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistr. 52, D-20246 Hamburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / 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:
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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