RT Journal Article
SR Electronic
T1 Autonomous CaMKII Can Promote either Long-Term Potentiation or Long-Term Depression, Depending on the State of T305/T306 Phosphorylation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8704
OP 8709
DO 10.1523/JNEUROSCI.0133-10.2010
VO 30
IS 26
A1 Hyun Jae Pi
A1 Nikolai Otmakhov
A1 David Lemelin
A1 Paul De Koninck
A1 John Lisman
YR 2010
UL http://www.jneurosci.org/content/30/26/8704.abstract
AB Ca2+/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.