Abstract

CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub.

Details

Title
The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms
Author
Incontro, Salvatore 1 ; Díaz-Alonso, Javier 1 ; Iafrati, Jillian 2 ; Vieira, Marta 3 ; Asensio, Cedric S 4   VIAFID ORCID Logo  ; Sohal, Vikaas S 2 ; Roche, Katherine W 3 ; Bender, Kevin J 5 ; Nicoll, Roger A 6 

1  Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA 
2  Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA 
3  Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA 
4  Department of Biological Sciences, University of Denver, Denver, CO, USA 
5  Department of Neurology, University of California, San Francisco, San Francisco, CA, USA 
6  Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA, USA 
Pages
1-21
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04439-7
ProQuest document ID
2044313362
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.