title: Local translation of TC10 is required for membrane expansion during axon outgrowth.
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.
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Neilia G
authors.initials: NG
authors.lastname: Gracias
authors.affiliation: 1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA [2].
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Shirkey-Son
authors.affiliation: 1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hengst
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C472451:Pard3 protein, rat; D012333:RNA, Messenger; D000076205:Ras Homolog Enriched in Brain Protein; C087693:Rheb protein, rat; D020932:Nerve Growth Factor; C546845:mTOR protein, rat; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases; C503262:Rhoq protein, rat; D020559:Monomeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins