CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action.

TitleCaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action.
Publication TypeJournal Article
Year of Publication2010
AuthorsPi HJae, Otmakhov N, El Gaamouch F, Lemelin D, De Koninck P, Lisman J
JournalProc Natl Acad Sci U S A
Volume107
Issue32
Pagination14437-42
Date Published2010 Aug 10
ISSN1091-6490
KeywordsAnimals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Dendritic Spines, Electrophysiology, Hippocampus, Microscopy, Confocal, Neuronal Plasticity, Phosphorylation, Rats, Rats, Sprague-Dawley, Synapses
Abstract

CaMKII is an abundant synaptic protein strongly implicated in plasticity. Overexpression of autonomous (T286D) CaMKII in CA1 hippocampal cells enhances synaptic strength if T305/T306 sites are not phosphorylated, but decreases synaptic strength if they are phosphorylated. It has generally been thought that spine size and synaptic strength covary; however, the ability of CaMKII and its various phosphorylation states to control spine size has not been previously examined. Using a unique method that allows the effects of overexpressed protein to be monitored over time, we found that all autonomous forms of CaMKII increase spine size. Thus, for instance, the T286D/T305D/T306D form increases spine size but decreases synaptic strength. Further evidence for such dissociation is provided by experiments with the T286D form that has been made catalytically dead. This form fails to enhance synaptic strength but increases spine size, presumably by a structural process. Thus very different mechanisms govern how CaMKII affects spine structure and synaptic function.

DOI10.1073/pnas.1009268107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20660727
PubMed Central IDPMC2922610
Grant ListR01 NS027337-19 / NS / NINDS NIH HHS / United States
R01 NS050944 / NS / NINDS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada

Funding

Our research endeavors are made possible by the following agencies:

Canadian Institutes of Health Research - Instituts de recherche en santé du Canada Fonds de recherche du Québec – Nature et technologies (FRQNT)Fonds de la recherche en santé du Québec NARSAD Natural Sciences and Engineering Research Council of Canada (NSERC) - Conseil de recherche en sciences naturelles et en génie du Canada (CRSNG)innovation.caHuman Frontier Science Program