Cell research, 2021-01, Vol.31 (1), p.37-51
2021
Details
- Autor(en) / Beteiligte
- Titel
- CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation
- Ist Teil von
- Cell research, 2021-01, Vol.31 (1), p.37-51
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Ca /calmodulin-dependent kinase IIα (CaMKIIα) is essential for synaptic plasticity and learning by decoding synaptic Ca oscillations. Despite decades of extensive research, new mechanisms underlying CaMKIIα's function in synapses are still being discovered. Here, we discover that Shank3 is a specific binding partner for autoinhibited CaMKIIα. We demonstrate that Shank3 and GluN2B, via combined actions of Ca and phosphatases, reciprocally bind to CaMKIIα. Under basal condition, CaMKIIα is recruited to the Shank3 subcompartment of postsynaptic density (PSD) via phase separation. Rise of Ca concentration induces GluN2B-mediated recruitment of active CaMKIIα and formation of the CaMKIIα/GluN2B/PSD-95 condensates, which are autonomously dispersed upon Ca removal. Protein phosphatases control the Ca -dependent shuttling of CaMKIIα between the two PSD subcompartments and PSD condensate formation. Activation of CaMKIIα further enlarges the PSD assembly and induces structural LTP. Thus, Ca -induced and phosphatase-checked shuttling of CaMKIIα between distinct PSD nano-domains can regulate phase separation-mediated PSD assembly and synaptic plasticity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1001-0602eISSN: 1748-7838DOI: 10.1038/s41422-020-00439-9Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7852677
- Format
- –
- Schlagworte
- Animals, Assembly, Binding Sites, Calcium - metabolism, Calcium ions, Calcium signalling, Calcium-binding protein, Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry, Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics, Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism, Calmodulin, Condensates, Disks Large Homolog 4 Protein - genetics, Disks Large Homolog 4 Protein - metabolism, HEK293 Cells, Humans, Kinases, Long-term potentiation, Mice, Molecular Docking Simulation, Nerve Tissue Proteins - chemistry, Nerve Tissue Proteins - metabolism, Neuronal Plasticity - physiology, Oscillations, Phase separation, Phosphatase, Phosphoprotein Phosphatases - metabolism, Phosphorylation, Plasticity, Postsynaptic density, Postsynaptic density proteins, Protein Binding, Rats, Receptors, N-Methyl-D-Aspartate - genetics, Receptors, N-Methyl-D-Aspartate - metabolism, SAP90-PSD95 Associated Proteins - metabolism, Synapses, Synaptic plasticity