Abstract
The surface of developing axons expands in a process mediated by the exocyst complex. The spatio-temporal regulation of the exocyst is only partially understood. Here we report that stimulated membrane enlargement in dorsal root ganglion (DRG) axons is triggered by intra-axonal synthesis of TC10, a small GTPase required for exocyst function. Induced membrane expansion and axon outgrowth are inhibited after axon-specific knockdown of TC10 mRNA. To determine the relationship of intra-axonal TC10 synthesis with the previously described stimulus-induced translation of the cytoskeletal regulator Par3, we investigate the signalling pathways controlling their local translation in response to NGF. Phosphoinositide 3-kinase (PI3K)-dependent activation of the Rheb-mTOR pathway triggers the simultaneous local synthesis of TC10 and Par3. These results reveal the importance of local translation in the control of membrane dynamics and demonstrate that localized, mTOR-dependent protein synthesis triggers the simultaneous activation of parallel pathways.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / drug effects
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Axons / metabolism*
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Carrier Proteins / drug effects
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cells, Cultured
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Ganglia, Spinal / cytology
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / metabolism*
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Monomeric GTP-Binding Proteins / drug effects
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Monomeric GTP-Binding Proteins / metabolism
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Nerve Growth Factor / pharmacology
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Nerve Tissue Proteins
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Neuropeptides / drug effects
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Neuropeptides / metabolism
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Phosphatidylinositol 3-Kinase / drug effects
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Phosphatidylinositol 3-Kinase / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism*
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Ras Homolog Enriched in Brain Protein
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Rats
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases / drug effects
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TOR Serine-Threonine Kinases / metabolism
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rho GTP-Binding Proteins / drug effects
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rho GTP-Binding Proteins / genetics*
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rho GTP-Binding Proteins / metabolism
Substances
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Carrier Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Pard3 protein, rat
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RNA, Messenger
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Ras Homolog Enriched in Brain Protein
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Rheb protein, rat
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Nerve Growth Factor
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mTOR protein, rat
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Phosphatidylinositol 3-Kinase
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TOR Serine-Threonine Kinases
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Rhoq protein, rat
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Monomeric GTP-Binding Proteins
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rho GTP-Binding Proteins