Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for midbrain dopamine (DA) neurons.GDNF exerts its biologic effects through a multi-component receptor system including a ligand binding receptor-the GDNF family receptor α1 (GFRα1) and a transmembrane signaling receptor-Ret.Recently,one kind of adhesion molecules-neural cell adhesion molecule had been identified as an alternative transmembrane signaling receptor for GDNF.The purpose of this study was to determine whether another transmembrane adhesion molecule-integrin might mediate the transmembrane signaling events of GDNF.We showed here that integrin (a)l was expressed in DA neurons in the substantia nigra (SN) of adult and aged rat,and the expression level of integrin β1 was lower in the aged rat SN than that in the adult.Further results in present study showed that GDNF could activate integrin β1-associated Shc pathway,and integrin β1 could form a complex with GFRα1 after GDNF treatment in our co-immunoprecipitation assays.To confirm the possibility of direct interaction between integrin and GFRα,we performed molecular modeling method in computer and the result showed that integrin I-domain could interact with GFRα.These results suggested that the integrin might be involved in the signaling events of GDNF.