Integrin beta1 is involved in the signaling of glial cell line-derived neurotrophic factor.
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 alpha (GFRalpha) 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 alpha and beta 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 beta1, increased after GDNF administration. Coimmunoprecipitation analysis demonstrated that integrin beta1 could form a complex with GFRalphal. The simulation of molecular modeling showed that four H-bonds were formed between integrin beta1 and GFRalpha. These data indicate that integrin beta1 is involved in the transmembrane signaling of GDNF and suggest that integrin beta1 may be an alternative signaling receptor for GDNF.
Cao
Jun-Ping
JP
Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, People's Republic of China.
Yu
Jing-Kao
JK
Li
Chong
C
Sun
Yu
Y
Yuan
Hong-Hua
HH
Wang
Hong-Jun
HJ
Gao
Dian-Shuai
DS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D006860:Hydrogen Bonding; D047468:Immunoprecipitation; D007267:Injections; D019012:Integrin beta1 / Q000502:physiology*; D008958:Models, Molecular; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013378:Substantia Nigra
D048868:Adaptor Proteins, Signal Transducing; C494989:Gfra1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D019012:Integrin beta1; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat