Title
Signaling Logic Of Activity-Triggered Dendritic Protein Synthesis: An Mtor Gate But Not A Feedback Switch
Abstract
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.
Year
DOI
Venue
2009
10.1371/journal.pcbi.1000287
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
signal transduction,calcium,positive feedback,protein synthesis
PI3K/AKT/mTOR pathway,Gating,Biology,Cell biology,Brain-derived neurotrophic factor,Positive feedback,Neurotrophic factors,Signal transduction,Synaptic plasticity,TOR Serine-Threonine Kinases
Journal
Volume
Issue
ISSN
5
2
1553-734X
Citations 
PageRank 
References 
5
1.09
3
Authors
2
Name
Order
Citations
PageRank
Pragati Jain151.09
Upinder S Bhalla233349.60