PMID- 24574971
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140325
LR  - 20220309
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 8
DP  - 2014
TI  - Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic 
      mRNA translation in neurons.
PG  - 35
LID - 10.3389/fncel.2014.00035 [doi]
LID - 35
AB  - Neuronal activity results in long lasting changes in synaptic structure and 
      function by regulating mRNA translation in dendrites. These activity dependent 
      events yield the synthesis of proteins known to be important for synaptic 
      modifications and diverse forms of synaptic plasticity. Worthy of note, there is 
      accumulating evidence that the eukaryotic Elongation Factor 2 Kinase 
      (eEF2K)/eukaryotic Elongation Factor 2 (eEF2) pathway may be strongly involved in 
      this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2, 
      resulting in a dramatic reduction of mRNA translation. eEF2K is activated by 
      elevated levels of calcium and binding of Calmodulin (CaM), hence its alternative 
      name calcium/CaM-dependent protein kinase III (CaMKIII). In dendrites, this 
      process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR) 
      activation. Interestingly, it has been shown that eEF2K can be activated in 
      dendrites by metabotropic glutamate receptor (mGluR) 1/5 signaling, as well. 
      Therefore, neuronal activity can induce local proteomic changes at the 
      postsynapse by altering eEF2K activity. Well-established targets of eEF2K in 
      dendrites include brain-derived neurotrophic factor (BDNF), activity-regulated 
      cytoskeletal-associated protein (Arc), the alpha subunit of calcium/CaM-dependent 
      protein kinase II (alphaCaMKII), and microtubule-associated protein 1B (MAP1B), all 
      of which have well-known functions in different forms of synaptic plasticity. In 
      this review we will give an overview of the involvement of the eEF2K/eEF2 pathway 
      at dendrites in regulating the translation of dendritic mRNA in the context of 
      altered NMDAR- and neuronal activity, and diverse forms of synaptic plasticity, 
      such as metabotropic glutamate receptor-dependent-long-term depression 
      (mGluR-LTD). For this, we draw on studies carried out both in vitro and in vivo.
FAU - Heise, Christopher
AU  - Heise C
AD  - CNR Institute of Neuroscience and Department of Biotechnology and Translational 
      Medicine, University of Milan Milan, Italy.
FAU - Gardoni, Fabrizio
AU  - Gardoni F
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan 
      Milan, Italy.
FAU - Culotta, Lorenza
AU  - Culotta L
AD  - CNR Institute of Neuroscience and Department of Biotechnology and Translational 
      Medicine, University of Milan Milan, Italy.
FAU - di Luca, Monica
AU  - di Luca M
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan 
      Milan, Italy.
FAU - Verpelli, Chiara
AU  - Verpelli C
AD  - CNR Institute of Neuroscience and Department of Biotechnology and Translational 
      Medicine, University of Milan Milan, Italy.
FAU - Sala, Carlo
AU  - Sala C
AD  - CNR Institute of Neuroscience and Department of Biotechnology and Translational 
      Medicine, University of Milan Milan, Italy ; Neuromuscular Diseases and 
      Neuroimmunology, Foundation Carlo Besta Neurological Institute Milan, Italy.
LA  - eng
GR  - GGP11095/TI_/Telethon/Italy
PT  - Journal Article
PT  - Review
DEP - 20140210
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC3918593
OTO - NOTNLM
OT  - dendrites
OT  - eEF2
OT  - eEF2K
OT  - neurons
OT  - synapses
OT  - synaptic plasticity
OT  - translation
EDAT- 2014/02/28 06:00
MHDA- 2014/02/28 06:01
PMCR- 2014/01/01
CRDT- 2014/02/28 06:00
PHST- 2013/09/09 00:00 [received]
PHST- 2014/01/23 00:00 [accepted]
PHST- 2014/02/28 06:00 [entrez]
PHST- 2014/02/28 06:00 [pubmed]
PHST- 2014/02/28 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2014.00035 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2014 Feb 10;8:35. doi: 10.3389/fncel.2014.00035. eCollection 
      2014.