Glycogen Synthase Kinase 3β-mediated Phosphorylation in the Most C-terminal Region of Protein Interacting with C Kinase 1 (PICK1) Regulates the Binding of PICK1 to Glutamate Receptor Subunit GluA2
| Autor: | Tomoe Ebihara, Miyuki Murayama, Akihiko Takashima, Kei Maruyama, Sosuke Yagishita |
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| Rok vydání: | 2015 |
| Předmět: |
Protein subunit
Molecular Sequence Data Glutamic Acid macromolecular substances AMPA receptor Biology Biochemistry Glycogen Synthase Kinase 3 Neurobiology GSK-3 Chlorocebus aethiops Serine Animals Immunoprecipitation Amino Acid Sequence Receptors AMPA Phosphorylation Molecular Biology Gene Glycogen Synthase Kinase 3 beta Sequence Homology Amino Acid Kinase Cell Membrane Glutamate receptor Nuclear Proteins Cell Biology Protein Structure Tertiary Rats Cytoskeletal Proteins Glycogen Synthase COS Cells Carrier Proteins PICK1 Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 290:29438-29448 |
| ISSN: | 0021-9258 |
| Popis: | Protein interacting with C kinase 1 (PICK1) is a synaptic protein interacting with the AMPA receptor subunits GluA2/3. The interaction between GluA2 and PICK1 is required for the removal of GluA2 from the synaptic plasma membrane during long-term depression (LTD). It has been suggested that glycogen synthase kinase 3β (GSK-3β) is activated during LTD, but the relationships between GluA2, PICK1, and GSK-3β are not well understood. In particular, the substrate(s) of GSK-3β have not yet been determined. Here we showed that PICK1 is a substrate of GSK-3β. We found that Ser(339), Ser(342), Ser(412), and Ser(416) of PICK1 were putative GSK-3β-mediated phosphorylation sites. Among these sites, Ser(416) played a crucial role in regulating the interaction between GluA2 and PICK1. We showed that replacing Ser(416) with Ala disrupted the GluA2-PICK1 interaction, whereas substituting Ser(416) with Glu or Asp retained this interaction. However, deletion of Ser(416) did not affect the GluA2-PICK1 interaction, and substitution of Ser(416) with Ala did not alter the PICK1-PICK1 interaction. Using image analysis in COS-7 cells with AcGFP1-fused PICK1, we showed that substitution of Ser(416) with Ala increased the formation of AcGFP1-positive clusters, suggesting an increase in the association of PICK1 with the membrane. This may have resulted in the dissociation of the GluA2-PICK1 complexes. Our results indicated that GSK-3β-mediated phosphorylation of PICK1 at Ser(416) was required for its association with the AMPA receptor subunit. Therefore, the GSK-3β-mediated phosphorylation of PICK1 may be a regulating factor during LTD induction. |
| Databáze: | OpenAIRE |
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