Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation.

TitleAutonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation.
Publication TypeJournal Article
Year of Publication2010
AuthorsPi HJae, Otmakhov N, Lemelin D, De Koninck P, Lisman J
JournalJ Neurosci
Volume30
Issue26
Pagination8704-9
Date Published2010 Jun 30
ISSN1529-2401
KeywordsAmino Acid Sequence, Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Excitatory Postsynaptic Potentials, Hippocampus, Holoenzymes, In Vitro Techniques, Long-Term Potentiation, Long-Term Synaptic Depression, Mutation, Neurons, Patch-Clamp Techniques, Phosphorylation, Synapses, Time Factors, Transfection
Abstract

Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a key mediator of long-term potentiation (LTP). Whereas acute intracellular injection of catalytically active CaMKII fragments saturates LTP (Lledo et al., 1995), an autonomously active form (T286D) of CaMKII holoenzyme expressed in transgenic mice did not saturate potentiation (Mayford et al., 1995). To better understand the role of the holoenzyme in the control of synaptic strength, we transfected hippocampal neurons with constructs encoding forms of CaMKII mimicking different phosphorylation states. Surprisingly, T286D not only failed to potentiate synaptic strength, but produced synaptic depression through an long-term depression (LTD)-like process. T305/T306 phosphorylation was critical for this depression because overexpression of the pseudophosphorylated form (T286D/T305D/T306D) caused depression that occluded LTD, and overexpression of an autonomous form in which T305/T306 could not be phosphorylated (T286D/T305A/T306A) prevented LTD (instead producing potentiation). Therefore, autonomous CaMKII can lead to either LTP or LTD, depending on the phosphorylation state of the control point, T305/T306.

DOI10.1523/JNEUROSCI.0133-10.2010
Alternate JournalJ. Neurosci.
PubMed ID20592192
PubMed Central IDPMC2903435
Grant ListR01 NS027337 / NS / NINDS NIH HHS / United States
R01 NS027337-19 / NS / NINDS NIH HHS / United States
R01 NS027337-19 / NS / NINDS NIH HHS / United States
R01 NS050944 / NS / NINDS NIH HHS / United States
R01 NS050944 / NS / NINDS NIH HHS / United States
R01 NS050944-01 / 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