Injured peripheral neurons successfully activate intrinsic signalingpathways to enable axon regeneration. We have previouslyshown that dorsal root ganglia (DRG) neurons activate themammalian target of rapamycin (mTOR) pathway followinginjury and that this activity enhances their axon growth capacity.mTOR plays a critical role in protein synthesis, but themTOR-dependent proteins enhancing the regenerative capacityof DRG neurons remain unknown. To identify proteins whoseexpression is regulated by injury in an mTOR-dependent manner,we analyzed the protein composition of DRGs from mice inwhich we genetically activated mTOR and from mice with orwithout a prior nerve injury. Quantitative label-free mass spectrometryanalyses revealed that the injury effects were correlatedwith mTOR activation. We identified a member of the solubleN-ethylmaleimide-sensitive factor attachment proteinreceptor (SNARE) family of proteins, syntaxin13, whose expressionwas increased by injury in an mTOR-dependent manner.Increased syntaxin13 levels in injured nerves resulted from localprotein synthesis and not axonal transport. Finally, knockdownof syntaxin13 in cultured DRG neurons prevented axon growthand regeneration. Together, these data suggest that syntaxin13translation is regulated bymTORin injured neurons to promoteaxon regeneration.
|Numero di pagine||13|
|Rivista||THE JOURNAL OF BIOLOGICAL CHEMISTRY|
|Stato di pubblicazione||Published - 2014|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Di Liberto, V., Di Liberto, V., Abe, N., Burlingame, A. L., Cho, Y., Michaelevski, I., Carlin, D., Guan, S., Cavalli, V., & Li, K. H. (2014). Syntaxin13 expression is regulated by mammalian target of rapamycin (mTOR) in injured neurons to promote axon regeneration. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 289, 15820-15832.