KEGG   PATHWAY: ko04361
Entry
ko04361                     Pathway                                
Name
Axon regeneration
Description
Many mature central nervous system (CNS) neurons in non-mammals, such as C. elegans, Drosophila, and zebrafish, are able to regenerate after injuries. The MAPK cascade, DLK-1/MKK-4/PMK-3/MAK2, is identified as an essential signaling pathway involved in axon regeneration in C. elegans. Calcium influx, which is triggered by axotomy, is implicated in DLK-1 activation. Another MAP kinase pathway, MLK-1/MEK-1/KGB-1, acts in parallel with the DLK-1 pathway to control growth-cone formation after axotomy. SVH-1, a homolog of the mammalian hepatocyte growth factor and its receptor SVH-2 function upstream of the MLK-1 pathway to promote axon regeneration. There are also inhibitors of regeneration, such as lin-12/Notch and efa-6. It is possible that the C. elegans pathways that inhibit regeneration function to stabilize the mature, uninjured nervous system.
Class
Organismal Systems; Development and regeneration
Pathway map
ko04361  Axon regeneration
ko04361

Orthology
K04851  voltage-dependent calcium channel L type alpha-1D
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K20105  cell death protein 4
K20106  cell death protein 3
K10693  RCR-type E3 ubiquitin transferase [EC:2.3.2.33]
K04422  mitogen-activated protein kinase kinase kinase 13 [EC:2.7.11.25]
K04430  mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04443  mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1]
K09442  SAM pointed domain-containing ETS transcription factor
K23479  CCAAT/enhancer binding protein (C/EBP), other
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K12494  PH and SEC7 domain-containing protein
K10393  kinesin family member 2/24
K23439  cytosolic carboxypeptidase protein 6 [EC:3.4.17.24]
K04459  dual specificity MAP kinase phosphatase [EC:3.1.3.16 3.1.3.48]
K23489  HGF/MSP/plasminogen-like protein
K04417  mitogen-activated protein kinase kinase kinase 9 [EC:2.7.11.25]
K04431  mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K09031  fos-like antigen, invertebrate
K15528  fatty acid amide hydrolase [EC:3.5.1.99]
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K06068  novel protein kinase C delta type [EC:2.7.11.13]
K04163  5-hydroxytryptamine receptor 7
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K04346  guanine nucleotide-binding protein subunit alpha-12
K07532  Rho guanine nucleotide exchange factor 12
K04513  Ras homolog gene family, member A
K00901  diacylglycerol kinase (ATP) [EC:2.7.1.107]
K08268  hypoxia-inducible factor 1 alpha
K00502  tryptophan 5-monooxygenase [EC:1.14.16.4]
K01593  aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28 4.1.1.105]
K04527  insulin receptor [EC:2.7.10.1]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K07203  serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K09408  forkhead box protein O3
K16336  syndecan 2
K06704  disintegrin and metalloproteinase domain-containing protein 10 [EC:3.4.24.81]
K02599  Notch 1
K04505  presenilin 1 [EC:3.4.23.-]
K04688  ribosomal protein S6 kinase beta [EC:2.7.11.1]
K07198  5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31]
K06839  slit 2
K05110  Eph receptor B1 [EC:2.7.10.1]
K06754  roundabout, axon guidance receptor 2
K06843  netrin 1
K23487  Ena/VASP-like protein
K23488  Ras-associated and pleckstrin homology domains-containing protein 1
K19862  NCK adaptor protein 2
K04392  Ras-related C3 botulinum toxin substrate 1
K16980  microRNA let-7
K12035  tripartite motif-containing protein 71 [EC:2.3.2.27]
K11593  eukaryotic translation initiation factor 2C
K23480  zinc finger protein 362/384
Compound
C00076  Calcium cation
C00078  L-Tryptophan
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C00643  5-Hydroxy-L-tryptophan
C00780  Serotonin
C11695  Anandamide
Reference
  Authors
Hisamoto N, Matsumoto K
  Title
Signal transduction cascades in axon regeneration: insights from C. elegans.
  Journal
Curr Opin Genet Dev 44:54-60 (2017)
DOI:10.1016/j.gde.2017.01.010
Reference
  Authors
Chen L, Chisholm AD
  Title
Axon regeneration mechanisms: insights from C. elegans.
  Journal
Trends Cell Biol 21:577-84 (2011)
DOI:10.1016/j.tcb.2011.08.003
Reference
  Authors
Saijilafu, Zhang BY, Zhou FQ
  Title
Signaling pathways that regulate axon regeneration.
  Journal
Neurosci Bull 29:411-20 (2013)
DOI:10.1007/s12264-013-1357-4
Reference
  Authors
El Bejjani R, Hammarlund M
  Title
Neural regeneration in Caenorhabditis elegans.
  Journal
Annu Rev Genet 46:499-513 (2012)
DOI:10.1146/annurev-genet-110711-155550
Reference
  Authors
Chisholm AD
  Title
Cytoskeletal dynamics in Caenorhabditis elegans axon regeneration.
  Journal
Annu Rev Cell Dev Biol 29:271-97 (2013)
DOI:10.1146/annurev-cellbio-101512-122311
Reference
  Authors
Hammarlund M, Jin Y
  Title
Axon regeneration in C. elegans.
  Journal
Curr Opin Neurobiol 27:199-207 (2014)
DOI:10.1016/j.conb.2014.04.001
Reference
  Authors
Pastuhov SI, Hisamoto N, Matsumoto K
  Title
MAP kinase cascades regulating axon regeneration in C. elegans.
  Journal
Proc Jpn Acad Ser B Phys Biol Sci 91:63-75 (2015)
DOI:10.2183/pjab.91.63
Reference
  Authors
Li C, Hisamoto N, Matsumoto K
  Title
Axon Regeneration Is Regulated by Ets-C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways.
  Journal
PLoS Genet 11:e1005603 (2015)
DOI:10.1371/journal.pgen.1005603
Reference
  Authors
Chen L, Chuang M, Koorman T, Boxem M, Jin Y, Chisholm AD
  Title
Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.
  Journal
Elife 4:e08695 (2015)
DOI:10.7554/eLife.08695
Reference
  Authors
Pastuhov SI, Fujiki K, Nix P, Kanao S, Bastiani M, Matsumoto K, Hisamoto N
  Title
Endocannabinoid-Goalpha signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqalpha-PKC-JNK signalling.
  Journal
Nat Commun 3:1136 (2012)
DOI:10.1038/ncomms2136
Reference
  Authors
Belin S, Norsworthy M, He Z
  Title
Independent control of aging and axon regeneration.
  Journal
Cell Metab 19:354-6 (2014)
DOI:10.1016/j.cmet.2014.02.014
Reference
  Authors
Byrne AB, Walradt T, Gardner KE, Hubbert A, Reinke V, Hammarlund M
  Title
Insulin/IGF1 signaling inhibits age-dependent axon regeneration.
  Journal
Neuron 81:561-73 (2014)
DOI:10.1016/j.neuron.2013.11.019
Reference
  Authors
Po MD, Calarco JA, Zhen M
  Title
Releasing the inner inhibition for axon regeneration.
  Journal
Neuron 73:207-9 (2012)
DOI:10.1016/j.neuron.2012.01.002
Reference
  Authors
El Bejjani R, Hammarlund M
  Title
Notch signaling inhibits axon regeneration.
  Journal
Neuron 73:268-78 (2012)
DOI:10.1016/j.neuron.2011.11.017
Reference
  Authors
Gabel CV, Antoine F, Chuang CF, Samuel AD, Chang C
  Title
Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans.
  Journal
Development 135:1129-36 (2008)
DOI:10.1242/dev.013995
Reference
  Authors
Hubert T, Wu Z, Chisholm AD, Jin Y
  Title
S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in Caenorhabditis elegans.
  Journal
J Neurosci 34:758-63 (2014)
DOI:10.1523/JNEUROSCI.2886-13.2014
Reference
  Authors
Zou Y, Chiu H, Zinovyeva A, Ambros V, Chuang CF, Chang C
  Title
Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers.
  Journal
Science 340:372-376 (2013)
DOI:10.1126/science.1231321
Reference
  Authors
Nix P, Bastiani M
  Title
Neuroscience. Heterochronic genes turn back the clock in old neurons.
  Journal
Science 340:282-3 (2013)
DOI:10.1126/science.1237921
Related
pathway
ko04150  mTOR signaling pathway
ko04910  Insulin signaling pathway
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