PMID- 29203851
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20211204
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 23
IP  - 1
DP  - 2018 Jan
TI  - Dynamic landscape of the local translation at activated synapses.
PG  - 107-114
LID - 10.1038/mp.2017.245 [doi]
AB  - The mammalian target of rapamycin (mTOR) signaling pathway is the central 
      regulator of cap-dependent translation at the synapse. Disturbances in mTOR 
      pathway have been associated with several neurological diseases, such as autism 
      and epilepsy. RNA-binding protein FMRP, a negative regulator of translation 
      initiation, is one of the key components of the local translation system. 
      Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and 
      dephosphorylation by PP2A phosphatase, respectively. S6 kinase and PP2A 
      phosphatase are activated in response to mGluR receptor stimulation through 
      different signaling pathways and at different rates. The dynamic aspects of this 
      system are poorly understood. We developed a mathematical model of FMRP-dependent 
      regulation of postsynaptic density (PSD) protein synthesis in response to mGluR 
      receptor stimulation and conducted in silico experiments to study the regulatory 
      circuit functioning. The modeling results revealed the possibility of generating 
      oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of 
      postsynaptic protein synthesis as well as the presence of multiple attractors in 
      a wide range of parameters of the local translation system. The results suggest 
      that autistic disorders associated with mTOR pathway hyperactivation may be due 
      to impaired proteome stability associated with the formation of complex dynamic 
      regimes of PSD protein synthesis in response to stimulation of mGluR receptors on 
      the postsynaptic membrane of excitatory synapses on pyramidal hippocampal cells.
FAU - Khlebodarova, T M
AU  - Khlebodarova TM
AD  - Federal Research Center Institute of Cytology and Genetics, Siberian Branch of 
      the Russian Academy of Sciences, Novosibirsk, Russia.
FAU - Kogai, V V
AU  - Kogai VV
AD  - Sobolev Institute of Mathematics, Siberian Branch of the Russian Academy of 
      Sciences, Novosibirsk, Russia.
AD  - Novosibirsk National Research State University, Novosibirsk, Russia.
FAU - Trifonova, E A
AU  - Trifonova EA
AD  - Federal Research Center Institute of Cytology and Genetics, Siberian Branch of 
      the Russian Academy of Sciences, Novosibirsk, Russia.
FAU - Likhoshvai, V A
AU  - Likhoshvai VA
AD  - Federal Research Center Institute of Cytology and Genetics, Siberian Branch of 
      the Russian Academy of Sciences, Novosibirsk, Russia.
AD  - Novosibirsk National Research State University, Novosibirsk, Russia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171205
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Fragile X Mental Retardation Protein/genetics/*metabolism
MH  - Humans
MH  - *Models, Theoretical
MH  - *Nonlinear Dynamics
MH  - Protein Biosynthesis/*physiology
MH  - Signal Transduction
MH  - Synapses/*pathology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5754473
COIS- The authors declare no conflict of interest.
EDAT- 2017/12/06 06:00
MHDA- 2018/12/18 06:00
PMCR- 2018/01/05
CRDT- 2017/12/06 06:00
PHST- 2017/10/05 00:00 [received]
PHST- 2017/10/09 00:00 [accepted]
PHST- 2017/12/06 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2017/12/06 06:00 [entrez]
PHST- 2018/01/05 00:00 [pmc-release]
AID - mp2017245 [pii]
AID - 10.1038/mp.2017.245 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2018 Jan;23(1):107-114. doi: 10.1038/mp.2017.245. Epub 2017 Dec 
      5.