| First Author | Perfitt TL | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 524 |
| Issue | 1 | Pages | 262-267 |
| PubMed ID | 31983435 | Mgi Jnum | J:296185 |
| Mgi Id | MGI:6468064 | Doi | 10.1016/j.bbrc.2020.01.089 |
| Citation | Perfitt TL, et al. (2020) CaMKIIalpha phosphorylation of Shank3 modulates ABI1-Shank3 interaction. Biochem Biophys Res Commun 524(1):262-267 |
| abstractText | 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 (CaMKIIalpha) also phosphorylates Shank3 at Ser685. Mutation of Ser685 to phospho-null alanine (S685A) prevented both CaMKIIalpha 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 CaMKIIalpha 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. |
