Local translation of TC10 is required for membrane expansion during axon outgrowth

Neilia G. Gracias, Nicole J. Shirkey-Son and Ulrich Hengst ()
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Neilia G. Gracias: The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center
Nicole J. Shirkey-Son: The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center
Ulrich Hengst: The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4506

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