PMID- 24032403
OWN - NLM
STAT- MEDLINE
DCOM- 20140512
LR  - 20211021
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 127
IP  - 5
DP  - 2013 Dec
TI  - Differential regulation of CaMKIIalpha interactions with mGluR5 and NMDA receptors by 
      Ca(2+) in neurons.
PG  - 620-31
LID - 10.1111/jnc.12434 [doi]
AB  - Two glutamate receptors, metabotropic glutamate receptor 5 (mGluR5), and 
      ionotropic NMDA receptors (NMDAR), functionally interact with each other to 
      regulate excitatory synaptic transmission in the mammalian brain. In exploring 
      molecular mechanisms underlying their interactions, we found that Ca(2+) 
      /calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) may play a central role. The 
      synapse-enriched CaMKIIalpha directly binds to the proximal region of intracellular C 
      terminal tails of mGluR5 in vitro. This binding is state-dependent: inactive 
      CaMKIIalpha binds to mGluR5 at a high level whereas the active form of the kinase 
      (following Ca(2+) /calmodulin binding and activation) loses its affinity for the 
      receptor. Ca(2+) also promotes calmodulin to bind to mGluR5 at a region 
      overlapping with the CaMKIIalpha-binding site, resulting in a competitive inhibition 
      of CaMKIIalpha binding to mGluR5. In rat striatal neurons, inactive CaMKIIalpha 
      constitutively binds to mGluR5. Activation of mGluR5 Ca(2+) -dependently 
      dissociates CaMKIIalpha from the receptor and simultaneously promotes CaMKIIalpha to bind 
      to the adjacent NMDAR GluN2B subunit, which enables CaMKIIalpha to phosphorylate 
      GluN2B at a CaMKIIalpha-sensitive site. Together, the long intracellular C-terminal 
      tail of mGluR5 seems to serve as a scaffolding domain to recruit and store 
      CaMKIIalpha within synapses. The mGluR5-dependent Ca(2+) transients differentially 
      regulate CaMKIIalpha interactions with mGluR5 and GluN2B in striatal neurons, which 
      may contribute to cross-talk between the two receptors. We show that activation 
      of mGluR5 with a selective agonist triggers intracellular Ca(2+) release in 
      striatal neurons. Released Ca(2+) dissociates preformed CaMKIIalpha from mGluR5 and 
      meanwhile promotes active CaMKIIalpha to bind to the adjacent NMDAR GluN2B subunit, 
      which enables CaMKIIalpha to phosphorylate GluN2B at a CaMKIIalpha-sensitive site. This 
      agonist-induced cascade seems to mediate crosstalk between mGluR5 and NMDA 
      receptors in neurons.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Jin, Dao-Zhong
AU  - Jin DZ
AD  - Department of Basic Medical Science, School of Medicine, University of 
      Missouri-Kansas City, Kansas City, Missouri, USA.
FAU - Guo, Ming-Lei
AU  - Guo ML
FAU - Xue, Bing
AU  - Xue B
FAU - Mao, Li-Min
AU  - Mao LM
FAU - Wang, John Q
AU  - Wang JQ
LA  - eng
GR  - DA10355/DA/NIDA NIH HHS/United States
GR  - R29 DA010355/DA/NIDA NIH HHS/United States
GR  - R01 DA010355/DA/NIDA NIH HHS/United States
GR  - MH61469/MH/NIMH NIH HHS/United States
GR  - R01 MH061469/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130917
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Calmodulin)
RN  - 0 (Camk2n1 protein, rat)
RN  - 0 (Carrier Proteins)
RN  - 0 (Grm5 protein, rat)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium-Binding Proteins
MH  - Calmodulin/metabolism
MH  - Carrier Proteins/*metabolism
MH  - Corpus Striatum/cytology/metabolism
MH  - Male
MH  - Molecular Sequence Data
MH  - Neurons/*metabolism
MH  - Nucleus Accumbens/cytology/metabolism
MH  - Phosphorylation/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Metabotropic Glutamate 5/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synaptic Transmission/physiology
PMC - PMC3933469
MID - NIHMS522550
OTO - NOTNLM
OT  - GluN2B
OT  - NR2B
OT  - calmodulin
OT  - mGluR
OT  - nucleus accumbens
OT  - striatum
COIS- Conflict of interest The authors declare that they have no conflict of interest.
EDAT- 2013/09/17 06:00
MHDA- 2014/05/13 06:00
PMCR- 2014/12/01
CRDT- 2013/09/17 06:00
PHST- 2013/05/31 00:00 [received]
PHST- 2013/08/05 00:00 [revised]
PHST- 2013/08/21 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/05/13 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 10.1111/jnc.12434 [doi]
PST - ppublish
SO  - J Neurochem. 2013 Dec;127(5):620-31. doi: 10.1111/jnc.12434. Epub 2013 Sep 17.