Syntaxin13 Expression Is Regulated by Mammalian Target of Rapamycin (mTOR) in Injured Neurons to Promote Axon Regeneration

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

doi:10.1074/jbc.m113.536607

Cited by 28 publications

(21 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Newly synthesized proteins that contribute to the regeneration process include cytoskeletal proteins (42) and membrane-associated proteins (43,44). Here we reveal that local translation of filamin A contributes to control of the spatial activity of HDAC5 in injured axons.…”

Section: Discussionmentioning

confidence: 89%

Filamin A Is Required in Injured Axons for HDAC5 Activity and Axon Regeneration

Cho

Park

Cavalli

2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Axon regeneration relies on HDAC5-dependent tubulin deacetylation at the site of injury. Results: Filamin A interacts with HDAC5 and is required for injury-induced tubulin deacetylation and axon regeneration. Conclusion: Filamin A is required in injured axons for HDAC5 activity and axon regeneration. Significance: Revealing the mechanisms involved in the spatial control of HDAC5 activity along the axon length is important to understand regenerative mechanisms in peripheral neurons.

show abstract

Section: Discussionmentioning

confidence: 89%

Filamin A Is Required in Injured Axons for HDAC5 Activity and Axon Regeneration

Cho

Park

Cavalli

2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, their expression is also required for the biogenesis of PMEL-positive premature melanosomes. Previous studies in non-melanocytes have shown that STX13 is required for recycling of transferrin receptor and other cargo to cell surface ( Prekeris et al, 1998 ), homotypic endosome fusion ( McBride et al, 1999 ), phagophore maturation ( Lu et al, 2013 ) and axon regeneration during nerve injury ( Cho et al, 2014 ). By contrast, VAMP7 is involved in the fusion of late endosomes with lysosomes ( Chaineau et al, 2009 ), delivery of GLUT1 to plasma membrane along with retromer ( Hesketh et al, 2014 ), membrane repair ( Rao et al, 2004 ), neurite outgrowth ( Martinez-Arca et al, 2000 ) and fusion of autophagosomes with lysosomes ( Fader et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis

Jani

Purushothaman

Rani

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

Melanosomes are a class of lysosome-related organelles produced by melanocytes. Biogenesis of melanosomes requires the transport of melanin-synthesizing enzymes from tubular recycling endosomes to maturing melanosomes. The SNARE proteins involved in these transport or fusion steps have been poorly studied. We found that depletion of syntaxin 13 (STX13, also known as STX12), a recycling endosomal Qa-SNARE, inhibits pigment granule maturation in melanocytes by rerouting the melanosomal proteins such as TYR and TYRP1 to lysosomes. Furthermore, live-cell imaging and electron microscopy studies showed that STX13 co-distributed with melanosomal cargo in the tubular-vesicular endosomes that are closely associated with the maturing melanosomes. STX family proteins contain an N-terminal regulatory domain, and deletion of this domain in STX13 increases both the SNARE activity in vivo and melanosome cargo transport and pigmentation, suggesting that STX13 acts as a fusion SNARE in melanosomal trafficking pathways. In addition, STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and its silencing blocks the melanosome maturation, reflecting a defect in endosome–melanosome fusion. Moreover, we show mutual dependency between STX13 and VAMP7 in regulating their localization for efficient cargo delivery to melanosomes.

show abstract

“…PI3K-Akt regulates local protein synthesis in the axon through the mTOR pathway, where adult CNS neurons require mTOR signaling for axon regeneration (31, 87, 88). Quantitative mass spectrometry identified syntaxin13 as a protein locally synthesized by activated mTOR in the axon (89). Knockdown of syntaxin13 in culture prevented axon growth and regeneration.…”

Section: Importance Of Proteomics In Identifying Mechanismsmentioning

confidence: 99%

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Niekerk

Tuszynski

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. Molecular & Cellular Proteomics

show abstract

Syntaxin13 Expression Is Regulated by Mammalian Target of Rapamycin (mTOR) in Injured Neurons to Promote Axon Regeneration

Cited by 28 publications

References 58 publications

Filamin A Is Required in Injured Axons for HDAC5 Activity and Axon Regeneration

Filamin A Is Required in Injured Axons for HDAC5 Activity and Axon Regeneration

STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Contact Info

Product

Resources

About