Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity
Summary: Calcium calmodulin-dependent kinase II (CaMKII) is critical for synaptic transmission and plasticity. Two major isoforms of CaMKII, CaMKIIα and CaMKIIβ, play distinct roles in synaptic transmission and long-term potentiation (LTP) with unknown mechanisms. Here, we show that the length of th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723001572 |
| _version_ | 1797895558560481280 |
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| author | Qixu Cai Xiumin Chen Shihan Zhu Roger A. Nicoll Mingjie Zhang |
| author_facet | Qixu Cai Xiumin Chen Shihan Zhu Roger A. Nicoll Mingjie Zhang |
| author_sort | Qixu Cai |
| collection | DOAJ |
| description | Summary: Calcium calmodulin-dependent kinase II (CaMKII) is critical for synaptic transmission and plasticity. Two major isoforms of CaMKII, CaMKIIα and CaMKIIβ, play distinct roles in synaptic transmission and long-term potentiation (LTP) with unknown mechanisms. Here, we show that the length of the unstructured linker between the kinase domain and the oligomerizing hub determines the ability of CaMKII to rescue the basal synaptic transmission and LTP defects caused by removal of both CaMKIIα and CaMKIIβ (double knockout [DKO]). Remarkably, although CaMKIIβ binds to GluN2B with a comparable affinity as CaMKIIα does, only CaMKIIα with the short linker forms robust dense clusters with GluN2B via phase separation. Lengthening the linker of CaMKIIα with unstructured “Gly-Gly-Ser” repeats impairs its phase separation with GluN2B, and the mutant enzyme cannot rescue the basal synaptic transmission and LTP defects of DKO mice. Our results suggest that the phase separation capacity of CaMKII with GluN2B is critical for its cellular functions in the brain. |
| first_indexed | 2024-04-10T07:27:43Z |
| format | Article |
| id | doaj.art-965a373f4a1848d2bcecd42d150388d7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T07:27:43Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-965a373f4a1848d2bcecd42d150388d72023-02-24T04:30:39ZengElsevierCell Reports2211-12472023-03-01423112146Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticityQixu Cai0Xiumin Chen1Shihan Zhu2Roger A. Nicoll3Mingjie Zhang4Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Department of Laboratory Medicine, School of Public Heath, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USADivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, ChinaDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding authorDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Corresponding authorSummary: Calcium calmodulin-dependent kinase II (CaMKII) is critical for synaptic transmission and plasticity. Two major isoforms of CaMKII, CaMKIIα and CaMKIIβ, play distinct roles in synaptic transmission and long-term potentiation (LTP) with unknown mechanisms. Here, we show that the length of the unstructured linker between the kinase domain and the oligomerizing hub determines the ability of CaMKII to rescue the basal synaptic transmission and LTP defects caused by removal of both CaMKIIα and CaMKIIβ (double knockout [DKO]). Remarkably, although CaMKIIβ binds to GluN2B with a comparable affinity as CaMKIIα does, only CaMKIIα with the short linker forms robust dense clusters with GluN2B via phase separation. Lengthening the linker of CaMKIIα with unstructured “Gly-Gly-Ser” repeats impairs its phase separation with GluN2B, and the mutant enzyme cannot rescue the basal synaptic transmission and LTP defects of DKO mice. Our results suggest that the phase separation capacity of CaMKII with GluN2B is critical for its cellular functions in the brain.http://www.sciencedirect.com/science/article/pii/S2211124723001572CP: Neuroscience |
| spellingShingle | Qixu Cai Xiumin Chen Shihan Zhu Roger A. Nicoll Mingjie Zhang Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity Cell Reports CP: Neuroscience |
| title | Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity |
| title_full | Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity |
| title_fullStr | Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity |
| title_full_unstemmed | Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity |
| title_short | Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity |
| title_sort | differential roles of camkii isoforms in phase separation with nmda receptors and in synaptic plasticity |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723001572 |
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