Autonomous CaMKII Can Promote either Long-Term Potentiation or Long-Term Depression, Depending on the State of T305/T306 Phosphorylation
- Hyun Jae Pi 1 , 2 ,
- Nikolai Otmakhov 2 ,
- David Lemelin 3 ,
- Paul De Koninck 3 , and
- John Lisman 2
- 1Quantitative Biology Program, Physics Department, and
- 2Volen Center for Complex Systems, Biology Department, Brandeis University, Waltham, Massachusetts 02454, and
- 3Centre de Recherche Université Laval Robert-Giffard, Quebec, Quebec G1J 2G3, Canada
- Correspondence should be addressed to John Lisman at the above address. lisman{at}brandeis.edu
Abstract
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.
- Copyright © 2010 the authors 0270-6474/10/308704-06$15.00/0
