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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sidorova, Yulia A. Bespalov, Maxim M. Magalhães, Ana Cathia Kulesskiy, Evgeny Ahonen-bishopp, Anni Tumova, Sarka Rauvala, Heikki Paveliev, Mikhail Saarma, Mart Rivera, Claudio |
| Description | Author Affiliation: Bespalov MM ( Institute of Biotechnology, Viikki Biocenter, and 2 Neuroscience Center, University of Helsinki, Helsinki 00014, Finland.) |
| Abstract | Glial cell line–derived neurotrophic factor (GDNF) family ligands (GFLs) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson’s disease. Soluble GFLs bind to a ligand-specific glycosylphosphatidylinositol-anchored coreceptor (GDNF family receptor α) and signal through the receptor tyrosine kinase RET. In this paper, we show that all immobilized matrix-bound GFLs, except persephin, use a fundamentally different receptor. They interact with syndecan-3, a transmembrane heparan sulfate (HS) proteoglycan, by binding to its HS chains with high affinity. GFL–syndecan-3 interaction mediates both cell spreading and neurite outgrowth with the involvement of Src kinase activation. GDNF promotes migration of cortical neurons in a syndecan-3–dependent manner, and in agreement, mice lacking syndecan-3 or GDNF have a reduced number of cortical γ-aminobutyric acid–releasing neurons, suggesting a central role for the two molecules in cortical development. Collectively, syndecan-3 may directly transduce GFL signals or serve as a coreceptor, presenting GFLs to the signaling receptor RET. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 192 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2011-01-10 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glial Cell Line-Derived Neurotrophic Factor Metabolism Nerve Tissue Proteins Neurturin Syndecan-3 Animals Cell Adhesion Drug Effects Cell Differentiation Cell Movement Cerebral Cortex Cytology Embryology Embryo, Mammalian Enzyme Activation Extracellular Matrix Pharmacology Heparin Immobilized Proteins Interneurons Ligands Mice Models, Biological Neurites Protein Binding Protein Transport Signal Transduction Src-Family Kinases Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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