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.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
authors.forename: Pragati
authors.initials: P
authors.lastname: Jain
authors.forename: Upinder S
authors.initials: US
authors.lastname: Bhalla
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium