CaMKIIα phosphorylation of Shank3 modulates ABI1-Shank3 interaction
| Autor: | Roger J. Colbran, Tyler L. Perfitt, Keeley L. Spiess, Philip E. Stauffer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Scaffold protein Biophysics Nerve Tissue Proteins Biochemistry Article Mice Phosphoserine 03 medical and health sciences 0302 clinical medicine Animals Humans Protein phosphorylation Phosphorylation Protein kinase A Molecular Biology Adaptor Proteins Signal Transducing Developmental maturation Chemistry Actin remodeling Cell Biology Cyclic AMP-Dependent Protein Kinases ABI1 Fusion protein Cell biology HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cattle Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Binding |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.01.089 |
| Popis: | Protein-protein interactions can be modulated by phosphorylation of either binding partner, thereby altering subcellular localization and/or physiological function. Shank3, a master postsynaptic scaffolding protein that controls the developmental maturation of excitatory synapses, was recently shown to be phosphorylated by Protein Kinase A (PKA) at Ser685 in vivo. Mutation of Shank3 Ser685 was shown to modulate the binding of Abelson interactor 1 (ABI1), a component of the WAVE regulatory complex for actin remodeling, but a direct effect of Ser685 phosphorylation on ABI1 binding was not investigated. Here, we demonstrate that Ca(2+)/calmodulin-dependent protein kinase II alpha (CaMKIIα) also phosphorylates Shank3 at Ser685. Mutation of Ser685 to phospho-null alanine (S685A) prevented both CaMKIIα and PKA phosphorylation of a GST-Shank3 fusion protein. The co-immunoprecipitation of ABI1 with Shank3 from HEK293 cell extracts is reduced by mutation of Ser685 to either Ala or Asp. However, pre-phosphorylation of GST-Shank3 by purified CaMKIIα significantly increased binding of ABI1, and this effect was abrogated by Ser685 to Ala mutation in GST-Shank3. Taken together, our data suggest that neuronal ABI1-Shank3 interactions may be convergently regulated by Shank3 Ser685 phosphorylation in response to both Ca(2+) and cAMP signaling, potentially modulating dendritic spine morphology. |
| Databáze: | OpenAIRE |
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