Back to Search
Start Over
Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs
- Source :
- Cell Reports, Vol 21, Iss 13, Pp 3781-3793 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 21
- Issue :
- 13
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.86e36bb9f2fb4ba8be4b301ce9acfea0
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.11.107