Characterization of the VPS10 Domain of SorLA/LR11 as Binding Site for the Neuropeptide HA
-
J. Lintzel
Abstract
The single transmembrane receptor sorLA/LR11 contains binding domains typical for the lowdensity 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 furinlike 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 receptorassociated protein RAP interacted both with the class A repeats and the VPS10 domain. The sorLA propeptide inhibited binding of HA to fulllength 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 HAstimulated 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.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Pigment Epithelium-Derived Factor (PEDF), a Serpin with Potent Anti-Angiogenic and Neurite Outgrowth-promoting Properties
- Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase
- Evidence for Haploinsufficiency of the Human HNF1α Gene Revealed by Functional Characterization of MODY3-Associated Mutations
- In vitro and in vivo Stability of the 2ζ2 Protein Complex of the Broad Host-Range Streptococcus pyogenes pSM19035 Addiction System
- Effects of Antineoplastic Agents on Cytoplasmic and Membrane-Bound Heat Shock Protein 70 (Hsp70) Levels
- Characterization of the VPS10 Domain of SorLA/LR11 as Binding Site for the Neuropeptide HA
- Substrate Specificity and Inhibitor Studies of a Membrane-Bound Ganglioside Sialidase Isolated from Human Brain Tissue
- Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
- Amylin-Induced Cytotoxicity Is Associated with Activation of Caspase-3 and MAP Kinases
- 2-Alkyl-3-Alkylamino-2H-Benzo- and Pyridothiadiazine 1,1-Dioxides: From K+ATP Channel Openers to Ca++ Channel Blockers?
- Pre-Loading of Chlorophyll Synthase with Tetraprenyl Diphosphate Is an Obligatory Step in Chlorophyll Biosynthesis
- Molecular and Immunological Characterization of Profilin from Mugwort Pollen
- The Archaeal Respiratory Supercomplex SoxM from S.acidocaldarius Combines Features of Quinole and Cytochrome c Oxidases
- Benzodiazepine Binding Studies on Living Cells: Application of Small Ligands for Fluorescence Correlation Spectroscopy
- Individual Recombinant Thyroglobulin Type-1 Domains Are Substrates for Lysosomal Cysteine Proteinases
- Characterization of Legumain
- Molecular Cloning and Chimerisation of an Inhibitory Anti-Cathepsin B Antibody and Its Expression in Chinese Hamster Ovary Cells
- Application of Peptides Containing the Cleavage Sequence of Pro-TNFα in Assessing TACE Activity of Whole Cells
Articles in the same Issue
- Pigment Epithelium-Derived Factor (PEDF), a Serpin with Potent Anti-Angiogenic and Neurite Outgrowth-promoting Properties
- Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase
- Evidence for Haploinsufficiency of the Human HNF1α Gene Revealed by Functional Characterization of MODY3-Associated Mutations
- In vitro and in vivo Stability of the 2ζ2 Protein Complex of the Broad Host-Range Streptococcus pyogenes pSM19035 Addiction System
- Effects of Antineoplastic Agents on Cytoplasmic and Membrane-Bound Heat Shock Protein 70 (Hsp70) Levels
- Characterization of the VPS10 Domain of SorLA/LR11 as Binding Site for the Neuropeptide HA
- Substrate Specificity and Inhibitor Studies of a Membrane-Bound Ganglioside Sialidase Isolated from Human Brain Tissue
- Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
- Amylin-Induced Cytotoxicity Is Associated with Activation of Caspase-3 and MAP Kinases
- 2-Alkyl-3-Alkylamino-2H-Benzo- and Pyridothiadiazine 1,1-Dioxides: From K+ATP Channel Openers to Ca++ Channel Blockers?
- Pre-Loading of Chlorophyll Synthase with Tetraprenyl Diphosphate Is an Obligatory Step in Chlorophyll Biosynthesis
- Molecular and Immunological Characterization of Profilin from Mugwort Pollen
- The Archaeal Respiratory Supercomplex SoxM from S.acidocaldarius Combines Features of Quinole and Cytochrome c Oxidases
- Benzodiazepine Binding Studies on Living Cells: Application of Small Ligands for Fluorescence Correlation Spectroscopy
- Individual Recombinant Thyroglobulin Type-1 Domains Are Substrates for Lysosomal Cysteine Proteinases
- Characterization of Legumain
- Molecular Cloning and Chimerisation of an Inhibitory Anti-Cathepsin B Antibody and Its Expression in Chinese Hamster Ovary Cells
- Application of Peptides Containing the Cleavage Sequence of Pro-TNFα in Assessing TACE Activity of Whole Cells
