Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch.
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 coordi...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-02-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC2647780?pdf=render |
| _version_ | 1818420045657669632 |
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| author | Pragati Jain Upinder S Bhalla |
| author_facet | Pragati Jain Upinder S Bhalla |
| author_sort | Pragati Jain |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T12:48:13Z |
| format | Article |
| id | doaj.art-e95ff98085064755a6477c92ab6966b4 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-14T12:48:13Z |
| publishDate | 2009-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-e95ff98085064755a6477c92ab6966b42022-12-21T23:00:44ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582009-02-0152e100028710.1371/journal.pcbi.1000287Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch.Pragati JainUpinder S BhallaChanges 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.http://europepmc.org/articles/PMC2647780?pdf=render |
| spellingShingle | Pragati Jain Upinder S Bhalla Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. PLoS Computational Biology |
| title | Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. |
| title_full | Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. |
| title_fullStr | Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. |
| title_full_unstemmed | Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. |
| title_short | Signaling logic of activity-triggered dendritic protein synthesis: an mTOR gate but not a feedback switch. |
| title_sort | signaling logic of activity triggered dendritic protein synthesis an mtor gate but not a feedback switch |
| url | http://europepmc.org/articles/PMC2647780?pdf=render |
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