PMID- 25446714
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20141209
IS  - 1095-8541 (Electronic)
IS  - 0022-5193 (Linking)
VI  - 365
DP  - 2015 Jan 21
TI  - Modelling the dynamics of CaMKII-NMDAR complex related to memory formation in 
      synapses: the possible roles of threonine 286 autophosphorylation of CaMKII in 
      long term potentiation.
PG  - 403-19
LID - S0022-5193(14)00633-X [pii]
LID - 10.1016/j.jtbi.2014.11.001 [doi]
AB  - A synaptic protein, Ca(2+)/Calmodulin dependent protein kinase II (CaMKII), has 
      complex state transitions and facilitates the emergence of long term potentiation 
      (LTP), which is highly correlated to memory formation. Two of the state 
      transitions are critical for LTP: (1) threonine 286 autophosphorylation of 
      CaMKII; and (2) binding to N-methyl-d-aspartate receptor (NMDAR) in the 
      postsynaptic density (PSD) to form CaMKII-NMDAR complex. Both of these state 
      transitions retain the activity of CaMKII when the induction signal disappears 
      which is very important for the long-lasting characteristics of LTP. However, the 
      possible relationships between the state transitions in the emergence of LTP are 
      not well understood. We develop a mathematical model of the formation of 
      CaMKII-NMDAR complex with the full state transitions of CaMKII, including the 
      autophosphorylation, based on ordinary differential equations. In addition, we 
      formulate a probabilistic framework for the binding between CaMKII and NMDAR. The 
      model gives accurate predictions of the behaviours of CaMKII in comparisons to 
      the experimental observations. Using the model, we show that: (1) the formation 
      of CaMKII-NMDAR complex is dependent not only on the binding affinity between 
      CaMKII and NMDAR, but also on the translocation of CaMKII into PSD; and (2) the 
      autophosphorylation is not a requirement for the formation of CaMKII-NMDAR 
      complex, but is important for the rapid formation of CaMKII-NMDAR complex during 
      LTP.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - He, Y
AU  - He Y
AD  - Centre for Advanced Computational Solutions (C-fACS), Department of Molecular 
      Biosciences, Lincoln University, Christchurch, New Zealand.
FAU - Kulasiri, D
AU  - Kulasiri D
AD  - Centre for Advanced Computational Solutions (C-fACS), Department of Molecular 
      Biosciences, Lincoln University, Christchurch, New Zealand. Electronic address: 
      don.kulasiri@lincoln.ac.nz.
FAU - Samarasinghe, S
AU  - Samarasinghe S
AD  - Centre for Advanced Computational Solutions (C-fACS), Department of Molecular 
      Biosciences, Lincoln University, Christchurch, New Zealand.
LA  - eng
PT  - Journal Article
DEP - 20141111
PL  - England
TA  - J Theor Biol
JT  - Journal of theoretical biology
JID - 0376342
RN  - 0 (Calmodulin)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/chemistry/*metabolism
MH  - Calmodulin/metabolism
MH  - Long-Term Potentiation/*physiology
MH  - Memory/*physiology
MH  - *Models, Biological
MH  - Phosphorylation
MH  - Post-Synaptic Density/metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Transport
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/*physiology
MH  - Threonine/*metabolism
OTO - NOTNLM
OT  - Autophosphorylation
OT  - CaMKII state transition
OT  - CaMKII-NMDAR complex
OT  - LTP
EDAT- 2014/12/03 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/04/17 00:00 [received]
PHST- 2014/10/31 00:00 [revised]
PHST- 2014/11/03 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - S0022-5193(14)00633-X [pii]
AID - 10.1016/j.jtbi.2014.11.001 [doi]
PST - ppublish
SO  - J Theor Biol. 2015 Jan 21;365:403-19. doi: 10.1016/j.jtbi.2014.11.001. Epub 2014 
      Nov 11.