PMID- 19242559
OWN - NLM
STAT- MEDLINE
DCOM- 20090427
LR  - 20220310
IS  - 1553-7358 (Electronic)
IS  - 1553-734X (Print)
IS  - 1553-734X (Linking)
VI  - 5
IP  - 2
DP  - 2009 Feb
TI  - Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate 
      but not a feedback switch.
PG  - e1000287
LID - 10.1371/journal.pcbi.1000287 [doi]
LID - e1000287
AB  - Changes in synaptic efficacy are believed to form the cellular basis for memory. 
      Protein synthesis in dendrites is needed to consolidate long-term synaptic 
      changes. Many signals converge to regulate dendritic protein synthesis, including 
      synaptic and cellular activity, and growth factors. The coordination of these 
      multiple inputs is especially intriguing because the synthetic and control 
      pathways themselves are among the synthesized proteins. We have modeled this 
      system to study its molecular logic and to understand how runaway feedback is 
      avoided. We show that growth factors such as brain-derived neurotrophic factor 
      (BDNF) gate activity-triggered protein synthesis via mammalian target of 
      rapamycin (mTOR). We also show that bistability is unlikely to arise from the 
      major protein synthesis pathways in our model, even though these include several 
      positive feedback loops. We propose that these gating and stability properties 
      may serve to suppress runaway activation of the pathway, while preserving the key 
      role of responsiveness to multiple sources of input.
FAU - Jain, Pragati
AU  - Jain P
AD  - National Centre for Biological Sciences, Tata Institute of Fundamental Research, 
      Bangalore, India.
FAU - Bhalla, Upinder S
AU  - Bhalla US
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090213
PL  - United States
TA  - PLoS Comput Biol
JT  - PLoS computational biology
JID - 101238922
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcium/metabolism
MH  - Dendrites/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nerve Tissue Proteins/*biosynthesis
MH  - Protein Kinases/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC2647780
COIS- The authors have declared that no competing interests exist.
EDAT- 2009/02/27 09:00
MHDA- 2009/04/28 09:00
PMCR- 2009/02/13
CRDT- 2009/02/27 09:00
PHST- 2008/10/14 00:00 [received]
PHST- 2009/01/05 00:00 [accepted]
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/04/28 09:00 [medline]
PHST- 2009/02/13 00:00 [pmc-release]
AID - 08-PLCB-RA-0921R3 [pii]
AID - 10.1371/journal.pcbi.1000287 [doi]
PST - ppublish
SO  - PLoS Comput Biol. 2009 Feb;5(2):e1000287. doi: 10.1371/journal.pcbi.1000287. Epub 
      2009 Feb 13.