Syntaxin13 expression is regulated by mammalian target of rapamycin (mTOR) in injured neurons to promote axon regeneration.

Valentina Di Liberto, Valentina Di Liberto, Namiko Abe, Alma L. Burlingame, Yongcheol Cho, Izhak Michaelevski, Dan Carlin, Shenheng Guan, Valeria Cavalli, Kathy H. Li

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Abstract

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.
Lingua originaleEnglish
pagine (da-a)15820-15832
Numero di pagine13
RivistaTHE JOURNAL OF BIOLOGICAL CHEMISTRY
Volume289
Stato di pubblicazionePublished - 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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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.