Fyn is a member of the Src family of nonreceptor tyrosine kinases and is broadly expressed in the CNS. As a synapse-enriched kinase， Fyn interacts with and phosphorylates local substrates to regulate synaptic transmission and plasticity， although our knowledge of specific targets of Fyn at synaptic sites remains incomplete and the accurate role of Fyn in regulating synaptic proteins is poorly understood. In this study， we initiated an effort to explore the interaction of Fyn with a metabotropic glutamate receptor (mGluR). We found that recombinant Fyn directly binds to mGluR1a at a consensus binding motif located in the intracellular C-terminus (CT) of mGluR1a . Similarly， endogenous Fyn interacts with ... More
Fyn is a member of the Src family of nonreceptor tyrosine kinases and is broadly expressed in the CNS. As a synapse-enriched kinase， Fyn interacts with and phosphorylates local substrates to regulate synaptic transmission and plasticity， although our knowledge of specific targets of Fyn at synaptic sites remains incomplete and the accurate role of Fyn in regulating synaptic proteins is poorly understood. In this study， we initiated an effort to explore the interaction of Fyn with a metabotropic glutamate receptor (mGluR). We found that recombinant Fyn directly binds to mGluR1a at a consensus binding motif located in the intracellular C-terminus (CT) of mGluR1a . Similarly， endogenous Fyn interacts with mGluR1a in adult rat cerebellar neurons . Active Fyn phosphorylates mGluR1a at a conserved tyrosine residue in the CT region. In cerebellar neurons and transfected HEK293T cells， the Fyn-mediated tyrosine phosphorylation of mGluR1a is constitutively active and acts to facilitate the surface expression of mGluR1a and to potentiate the mGluR1a postreceptor signaling. These results support mGluR1a to be a novel substrate of Fyn. Fyn， by binding to and phosphorylating mGluR1a， potentiates surface expression and signaling of the receptors.
