151. Integrin β1 is involved in the signaling of glial cell line-derived neurotrophic factor
- Author
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Hong-Jun Wang, Honghua Yuan, Dianshuai Gao, Junping Cao, Chong Li, Jing-Kao Yu, and Yu Sun
- Subjects
Models, Molecular ,Glial Cell Line-Derived Neurotrophic Factor Receptors ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,animal diseases ,Integrin ,CD49c ,Injections ,Collagen receptor ,Rats, Sprague-Dawley ,Random Allocation ,Neurotrophic factors ,Protein Interaction Mapping ,Glial cell line-derived neurotrophic factor ,Animals ,Immunoprecipitation ,Glial Cell Line-Derived Neurotrophic Factor ,Phosphorylation ,Adaptor Proteins, Signal Transducing ,biology ,urogenital system ,Integrin beta1 ,General Neuroscience ,Hydrogen Bonding ,Rats ,Cell biology ,Substantia Nigra ,Shc Signaling Adaptor Proteins ,nervous system ,Integrin alpha M ,Focal Adhesion Kinase 1 ,biology.protein ,Integrin, beta 6 ,Protein Processing, Post-Translational ,GDNF family of ligands ,Signal Transduction - Abstract
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for the substantia nigra (SN) dopamine (DA) neurons. The transmembrane signaling of GDNF is mediated by a unique receptor system, including the ligand binding receptor GDNF family receptor α (GFRα) and the transmembrane signaling receptor Ret or neural cell adhesion molecule-140 (NCAM-140). Here, we found that another transmembrane cell adhesion molecule, integrin, a heterodimer consisting of α and β subunits, also mediates the transmembrane signaling of GDNF. The results showed that the level of phosphorylated Src homology 2 domain containing (Shc), which was associated with the cytoplasmic domain of integrin β1, increased after GDNF administration. Coimmunoprecipitation analysis demonstrated that integrin β1 could form a complex with GFRαl. The simulation of molecular modeling showed that four H-bonds were formed between integrin β1 and GFRα. These data indicate that integrin β1 is involved in the transmembrane signaling of GDNF and suggest that integrin β1 may be an alternative signaling receptor for GDNF. J. Comp. Neurol. 509:203–210, 2008. © 2008 Wiley-Liss, Inc.
- Published
- 2008