Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Phosphorylation of spinophilin modulates its interaction with actin filaments.

Spinophilin is a protein phosphatase 1 (PP1)- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology. We report that spinophilin is phosphorylated in vitro by protein kinase A (PKA). Phosphorylation of spinophilin was stimulated by treatment of neostriatal neurons with a dopamine D1 receptor agonist or with forskolin, consistent with spinophilin being a substrate for PKA in intact cells. Using tryptic phosphopeptide mapping, site-directed mutagenesis, and microsequencing analysis, we identified two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. Following subcellular fractionation, unphosphorylated spinophilin was enriched in the postsynaptic density, whereas a pool of phosphorylated spinophilin was found in the cytosol. F-actin co-sedimentation and overlay analysis revealed that phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged. Taken together, our studies suggest that phosphorylation of spinophilin by PKA modulates the anchoring of the spinophilin-PP1 complex within dendritic spines, thereby likely contributing to the efficacy and plasticity of synaptic transmission.

Pubmed ID: 12417592


  • Hsieh-Wilson LC
  • Benfenati F
  • Snyder GL
  • Allen PB
  • Nairn AC
  • Greengard P


The Journal of biological chemistry

Publication Data

January 10, 2003

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA10044
  • Agency: NIMH NIH HHS, Id: MH40899
  • Agency: NIDA NIH HHS, Id: P01 DA010044

Mesh Terms

  • Actins
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Male
  • Microfilament Proteins
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Protein Phosphatase 1
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1
  • Serine