PMID- 25609615
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20220129
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 35
IP  - 3
DP  - 2015 Jan 21
TI  - BDNF stimulation of protein synthesis in cortical neurons requires the MAP 
      kinase-interacting kinase MNK1.
PG  - 972-84
LID - 10.1523/JNEUROSCI.2641-14.2015 [doi]
AB  - Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years, 
      their roles in the regulation of protein synthesis have remained obscure. Here, 
      we explore the involvement of the MNKs in brain-derived neurotrophic factor 
      (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a 
      combination of pharmacological and genetic approaches, we show that BDNF-induced 
      upregulation of protein synthesis requires MEK/ERK signaling and the downstream 
      kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E. 
      Translation initiation is mediated by the interaction of eIF4E with the m(7)GTP 
      cap of mRNA and with eIF4G. The latter interaction is inhibited by the 
      interactions of eIF4E with partner proteins, such as CYFIP1, which acts as a 
      translational repressor. We find that BDNF induces the release of CYFIP1 from 
      eIF4E, and that this depends on MNK1. Finally, using a novel combination of 
      BONCAT and SILAC, we identify a subset of proteins whose synthesis is upregulated 
      by BDNF signaling via MNK1 in neurons. Interestingly, this subset of 
      MNK1-sensitive proteins is enriched for functions involved in neurotransmission 
      and synaptic plasticity. Additionally, we find significant overlap between our 
      subset of proteins whose synthesis is regulated by MNK1 and those encoded by 
      known FMRP-binding mRNAs. Together, our data implicate MNK1 as a key component of 
      BDNF-mediated translational regulation in neurons.
CI  - Copyright (c) 2015 Genheden et al.
FAU - Genheden, Maja
AU  - Genheden M
AD  - Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, 
      United Kingdom.
FAU - Kenney, Justin W
AU  - Kenney JW
AD  - Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, 
      United Kingdom.
FAU - Johnston, Harvey E
AU  - Johnston HE
AUID- ORCID: 0000-0001-7032-0227
AD  - Cancer Sciences and CES Units, Faculty of Medicine, University of Southampton, 
      Southampton General Hospital, Southampton, SO16 6YD, United Kingdom, and Centre 
      for Proteomic Research, Institute for Life Sciences, University of Southampton, 
      Highfield Campus, Southampton, SO17 1BJ, United Kingdom.
FAU - Manousopoulou, Antigoni
AU  - Manousopoulou A
AD  - Cancer Sciences and CES Units, Faculty of Medicine, University of Southampton, 
      Southampton General Hospital, Southampton, SO16 6YD, United Kingdom, and Centre 
      for Proteomic Research, Institute for Life Sciences, University of Southampton, 
      Highfield Campus, Southampton, SO17 1BJ, United Kingdom.
FAU - Garbis, Spiros D
AU  - Garbis SD
AD  - Cancer Sciences and CES Units, Faculty of Medicine, University of Southampton, 
      Southampton General Hospital, Southampton, SO16 6YD, United Kingdom, and Centre 
      for Proteomic Research, Institute for Life Sciences, University of Southampton, 
      Highfield Campus, Southampton, SO17 1BJ, United Kingdom.
FAU - Proud, Christopher G
AU  - Proud CG
AUID- ORCID: 0000-0003-0704-6442
AD  - Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, 
      United Kingdom, Christopher.proud@sahmri.com.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - BB/I004483/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - 086688/WT_/Wellcome Trust/United Kingdom
GR  - BB/I004483/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyfip1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.1.- (Mknk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Mice
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Biosynthesis/*drug effects/physiology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Up-Regulation/drug effects
PMC - PMC4300335
OTO - NOTNLM
OT  - BDNF
OT  - BONCAT
OT  - CYFIP1
OT  - MNK
OT  - SILAC
OT  - eIF4E
EDAT- 2015/01/23 06:00
MHDA- 2015/03/25 06:00
PMCR- 2015/01/21
CRDT- 2015/01/23 06:00
PHST- 2015/01/23 06:00 [entrez]
PHST- 2015/01/23 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
PHST- 2015/01/21 00:00 [pmc-release]
AID - 35/3/972 [pii]
AID - 2641-14 [pii]
AID - 10.1523/JNEUROSCI.2641-14.2015 [doi]
PST - ppublish
SO  - J Neurosci. 2015 Jan 21;35(3):972-84. doi: 10.1523/JNEUROSCI.2641-14.2015.