The brake within: Mechanisms of intrinsic regulation of axon growth featuring the Cdh1-APC pathway

[1] Huber A.B., Kolodkin A.L., Ginty D.D., Cloutier J.F., Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance, Annu. Rev. Neurosci., 2003, 26, 509–563 http://dx.doi.org/10.1146/annurev.neuro.26.010302.08113910.1146/annurev.neuro.26.010302.081139Search in Google Scholar PubMed

[2] Dickson B.J., Molecular mechanisms of axon guidance, Science, 2002, 298, 1959–1964 http://dx.doi.org/10.1126/science.107216510.1126/science.1072165Search in Google Scholar PubMed

[3] Tessier-Lavigne M., Goodman C.S., The molecular biology of axon guidance, Science, 1996, 274, 1123–1133 http://dx.doi.org/10.1126/science.274.5290.112310.1126/science.274.5290.1123Search in Google Scholar PubMed

[4] Derijck A.A., Van Erp S., Pasterkamp R.J., Semaphorin signaling: molecular switches at the midline, Trends Cell Biol., 2010, 20, 568–576 http://dx.doi.org/10.1016/j.tcb.2010.06.00710.1016/j.tcb.2010.06.007Search in Google Scholar PubMed

[5] Rajasekharan S., Kennedy T.E., The netrin protein family, Genome Biol., 2009, 10, 239 http://dx.doi.org/10.1186/gb-2009-10-9-23910.1186/gb-2009-10-9-239Search in Google Scholar PubMed PubMed Central

[6] He Z., Wang K.C., Koprivica V., Ming G., Song H.J., Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system, Sci. STKE, 2002, 2002, re1 http://dx.doi.org/10.1126/stke.2002.119.re110.1126/stke.2002.119.re1Search in Google Scholar PubMed

[7] Nguyen-Ba-Charvet K.T., Chedotal A., Role of Slit proteins in the vertebrate brain, J. Physiol., Paris, 2002, 96, 91–98 http://dx.doi.org/10.1016/S0928-4257(01)00084-510.1016/S0928-4257(01)00084-5Search in Google Scholar PubMed

[8] Dickson B.J., Gilestro G.F., Regulation of commissural axon pathfinding by slit and its Robo receptors, Annu. Rev. Cell Dev. Biol., 2006, 22, 651–675 http://dx.doi.org/10.1146/annurev.cellbio.21.090704.15123410.1146/annurev.cellbio.21.090704.151234Search in Google Scholar PubMed

[9] Markus A., Patel T.D., Snider W.D., Neurotrophic factors and axonal growth, Curr. Opin. Neurobiol., 2002, 12, 523–531 http://dx.doi.org/10.1016/S0959-4388(02)00372-010.1016/S0959-4388(02)00372-0Search in Google Scholar

[10] Huang E.J., Reichardt L.F., Neurotrophins: roles in neuronal development and function, Annu. Rev. Neurosci., 2001, 24, 677–736 http://dx.doi.org/10.1146/annurev.neuro.24.1.67710.1146/annurev.neuro.24.1.677Search in Google Scholar PubMed PubMed Central

[11] Arévalo J.C., Chao M.V., Axonal growth: where neurotrophins meet Wnts, Curr. Opin. Cell Biol., 2005, 17, 112–115 http://dx.doi.org/10.1016/j.ceb.2005.01.00410.1016/j.ceb.2005.01.004Search in Google Scholar PubMed

[12] Klein R., Eph/ephrin signalling during development, Development, 2012, 139, 4105–4109 http://dx.doi.org/10.1242/dev.07499710.1242/dev.074997Search in Google Scholar PubMed

[13] Zhou F.Q., Zhong J., Snider W.D., Extracellular crosstalk: when GDNF meets N-CAM, Cell, 2003, 113, 814–815 http://dx.doi.org/10.1016/S0092-8674(03)00467-710.1016/S0092-8674(03)00467-7Search in Google Scholar PubMed

[14] Schmid R.S., Maness P.F., L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth, Curr. Opin. Neurobiol., 2008, 18, 245–250 http://dx.doi.org/10.1016/j.conb.2008.07.01510.1016/j.conb.2008.07.015Search in Google Scholar PubMed PubMed Central

[15] Bray G.M., Villegas-Perez M.P., Vidal-Sanz M., Carter D.A., Aguayo A.J., Neuronal and nonneuronal influences on retinal ganglion cell survival, axonal regrowth, and connectivity after axotomy, Ann. NY Acad. Sci., 1991, 633, 214–228 http://dx.doi.org/10.1111/j.1749-6632.1991.tb15613.x10.1111/j.1749-6632.1991.tb15613.xSearch in Google Scholar PubMed

[16] Goldberg J.L., Barres B.A., The relationship between neuronal survival and regeneration, Annu. Rev. Neurosci., 2000, 23, 579–612 http://dx.doi.org/10.1146/annurev.neuro.23.1.57910.1146/annurev.neuro.23.1.579Search in Google Scholar PubMed

[17] Schwab M.E., Nogo and axon regeneration, Curr. Opin. Neurobiol., 2004, 14, 118–124 http://dx.doi.org/10.1016/j.conb.2004.01.00410.1016/j.conb.2004.01.004Search in Google Scholar PubMed

[18] Strittmatter S.M., Modulation of axonal regeneration in neurodegenerative disease: focus on Nogo, J. Mol. Neurosci., 2002, 19, 117–121 http://dx.doi.org/10.1007/s12031-002-0021-710.1007/s12031-002-0021-7Search in Google Scholar PubMed

[19] Yiu G., He Z., Glial inhibition of CNS axon regeneration, Nat. Rev. Neurosci., 2006, 7, 617–627 http://dx.doi.org/10.1038/nrn195610.1038/nrn1956Search in Google Scholar PubMed PubMed Central

[20] Fournier A.E., Strittmatter S.M., Repulsive factors and axon regeneration in the CNS, Curr. Opin. Neurobiol., 2001, 11, 89–94 http://dx.doi.org/10.1016/S0959-4388(00)00178-110.1016/S0959-4388(00)00178-1Search in Google Scholar PubMed

[21] Busch S.A., Silver J., The role of extracellular matrix in CNS regeneration, Curr. Opin. Neurobiol., 2007, 17, 120–127 http://dx.doi.org/10.1016/j.conb.2006.09.00410.1016/j.conb.2006.09.004Search in Google Scholar PubMed

[22] David S., Zarruk J.G., Ghasemlou N., Inflammatory pathways in spinal cord injury, Int. Rev. Neurobiol., 2012, 106, 127–152 http://dx.doi.org/10.1016/B978-0-12-407178-0.00006-510.1016/B978-0-12-407178-0.00006-5Search in Google Scholar PubMed

[23] Carulli D., Laabs T., Geller H.M., Fawcett J.W., Chondroitin sulfate proteoglycans in neural development and regeneration, Curr. Opin. Neurobiol., 2005, 15, 116–120 http://dx.doi.org/10.1016/j.conb.2005.03.01810.1016/j.conb.2005.03.018Search in Google Scholar

[24] Dickson B.J., Rho GTPases in growth cone guidance, Curr. Opin. Neurobiol., 2001, 11, 103–110 http://dx.doi.org/10.1016/S0959-4388(00)00180-X10.1016/S0959-4388(00)00180-XSearch in Google Scholar

[25] Govek E.E., Newey S.E., Van Aelst L., The role of the Rho GTPases in neuronal development, Genes Dev., 2005, 19, 1–49 http://dx.doi.org/10.1101/gad.125640510.1101/gad.1256405Search in Google Scholar PubMed

[26] Luo L., Rho GTPases in neuronal morphogenesis, Nat. Rev. Neurosci., 2000, 1, 173–180 http://dx.doi.org/10.1038/3504454710.1038/35044547Search in Google Scholar PubMed

[27] Dickendesher T.L., Baldwin K.T., Mironova Y.A., Koriyama Y., Raiker S.J., Askew K.L., et al., NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans, Nat. Neurosci., 2012, 15, 703–712 http://dx.doi.org/10.1038/nn.307010.1038/nn.3070Search in Google Scholar PubMed PubMed Central

[28] Niederost B., Oertle T., Fritsche J., McKinney R.A., Bandtlow C.E., Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1, J. Neurosci., 2002, 22, 10368–10376 10.1523/JNEUROSCI.22-23-10368.2002Search in Google Scholar PubMed PubMed Central

[29] Kopp M.A., Liebscher T., Niedeggen A., Laufer S., Brommer B., Jungehulsing G.J., et al., Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury, Cell Tissue Res., 2012, 349, 119–132 http://dx.doi.org/10.1007/s00441-012-1334-710.1007/s00441-012-1334-7Search in Google Scholar PubMed PubMed Central

[30] Kubo T., Yamashita T., Rho-ROCK inhibitors for the treatment of CNS injury, Recent Pat. CNS Drug Discov., 2007, 2, 173–179 http://dx.doi.org/10.2174/15748890778241173810.2174/157488907782411738Search in Google Scholar PubMed

[31] McKerracher L., Ferraro G.B., Fournier A.E., Rho signaling and axon regeneration, Int. Rev. Neurobiol., 2012, 105, 117–140 http://dx.doi.org/10.1016/B978-0-12-398309-1.00007-X10.1016/B978-0-12-398309-1.00007-XSearch in Google Scholar PubMed

[32] Filbin M.T., Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS, Nat. Rev. Neurosci., 2003, 4, 703–713 http://dx.doi.org/10.1038/nrn119510.1038/nrn1195Search in Google Scholar PubMed

[33] Benowitz L., Yin Y., Rewiring the injured CNS: lessons from the optic nerve, Exp. Neurol., 2008, 209, 389–398 http://dx.doi.org/10.1016/j.expneurol.2007.05.02510.1016/j.expneurol.2007.05.025Search in Google Scholar PubMed PubMed Central

[34] Giger R.J., Hollis E.R. 2nd, Tuszynski M.H., Guidance molecules in axon regeneration, Cold Spring Harb. Perspect. Biol., 2010, 2, a001867 http://dx.doi.org/10.1101/cshperspect.a00186710.1101/cshperspect.a001867Search in Google Scholar PubMed PubMed Central

[35] Chen D.F., Jhaveri S., Schneider G.E., Intrinsic changes in developing retinal neurons result in regenerative failure of their axons, Proc. Natl. Acad. Sci. USA, 1995, 92, 7287–7291 http://dx.doi.org/10.1073/pnas.92.16.728710.1073/pnas.92.16.7287Search in Google Scholar PubMed PubMed Central

[36] Goldberg J.L., Klassen M.P., Hua Y., Barres B.A., Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells, Science, 2002, 296, 1860–1864 http://dx.doi.org/10.1126/science.106842810.1126/science.1068428Search in Google Scholar PubMed

[37] de la Torre-Ubieta L., Bonni A., Transcriptional regulation of neuronal polarity and morphogenesis in the mammalian brain, Neuron, 2011, 72, 22–40 http://dx.doi.org/10.1016/j.neuron.2011.09.01810.1016/j.neuron.2011.09.018Search in Google Scholar PubMed PubMed Central

[38] Butler S.J., Tear G., Getting axons onto the right path: the role of transcription factors in axon guidance, Development, 2007, 134, 439–448 http://dx.doi.org/10.1242/dev.0276210.1242/dev.02762Search in Google Scholar PubMed

[39] Polleux F., Ince-Dunn G., Ghosh A., Transcriptional regulation of vertebrate axon guidance and synapse formation, Nat. Rev. Neurosci., 2007, 8, 331–340 http://dx.doi.org/10.1038/nrn211810.1038/nrn2118Search in Google Scholar PubMed

[40] Theil T., Frain M., Gilardi-Hebenstreit P., Flenniken A., Charnay P., Wilkinson D.G., Segmental expression of the EphA4 (Sek-1) receptor tyrosine kinase in the hindbrain is under direct transcriptional control of Krox-20, Development, 1998, 125, 443–452 10.1242/dev.125.3.443Search in Google Scholar PubMed

[41] Kania A., Jessell T.M., Topographic motor projections in the limb imposed by LIM homeodomain protein regulation of ephrin-A: EphA interactions, Neuron, 2003, 38, 581–596 http://dx.doi.org/10.1016/S0896-6273(03)00292-710.1016/S0896-6273(03)00292-7Search in Google Scholar

[42] Marmigere F., Montelius A., Wegner M., Groner Y., Reichardt L.F., Ernfors P., The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons, Nat. Neurosci., 2006, 9, 180–187 http://dx.doi.org/10.1038/nn163110.1038/nn1631Search in Google Scholar PubMed PubMed Central

[43] Moore D.L., Blackmore M.G., Hu Y., Kaestner K.H., Bixby J.L., Lemmon V.P., et al., KLF family members regulate intrinsic axon regeneration ability, Science, 2009, 326, 298–301 http://dx.doi.org/10.1126/science.117573710.1126/science.1175737Search in Google Scholar PubMed PubMed Central

[44] Zou H., Ho C., Wong K., Tessier-Lavigne M., Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons, J. Neurosci., 2009, 29, 7116–7123 http://dx.doi.org/10.1523/JNEUROSCI.5397-08.200910.1523/JNEUROSCI.5397-08.2009Search in Google Scholar PubMed PubMed Central

[45] Parikh P., Hao Y., Hosseinkhani M., Patil S.B., Huntley G.W., Tessier-Lavigne M., et al., Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons, Proc. Natl. Acad. Sci. USA, 2011, 108, E99–107 http://dx.doi.org/10.1073/pnas.110042610810.1073/pnas.1100426108Search in Google Scholar PubMed PubMed Central

[46] Park K.K., Liu K., Hu Y., Smith P.D., Wang C., Cai B., et al., Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway, Science, 2008, 322, 963–966 http://dx.doi.org/10.1126/science.116156610.1126/science.1161566Search in Google Scholar PubMed PubMed Central

[47] Smith P.D., Sun F., Park K.K., Cai B., Wang C., Kuwako K., et al., SOCS3 deletion promotes optic nerve regeneration in vivo, Neuron, 2009, 64, 617–623 http://dx.doi.org/10.1016/j.neuron.2009.11.02110.1016/j.neuron.2009.11.021Search in Google Scholar PubMed PubMed Central

[48] Sun F., Park K.K., Belin S., Wang D., Lu T., Chen G., et al., Sustained axon regeneration induced by co-deletion of PTEN and SOCS3, Nature, 2011, 480, 372–375 http://dx.doi.org/10.1038/nature1059410.1038/nature10594Search in Google Scholar PubMed PubMed Central

[49] Luo X., Park K.K., Neuron-intrinsic inhibitors of axon regeneration: PTEN and SOCS3, Int. Rev. Neurobiol., 2012, 105, 141–173 http://dx.doi.org/10.1016/B978-0-12-398309-1.00008-110.1016/B978-0-12-398309-1.00008-1Search in Google Scholar PubMed

[50] Erturk A., Hellal F., Enes J., Bradke F., Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration, J. Neurosci., 2007, 27, 9169–9180 http://dx.doi.org/10.1523/JNEUROSCI.0612-07.200710.1523/JNEUROSCI.0612-07.2007Search in Google Scholar PubMed PubMed Central

[51] Hellal F., Hurtado A., Ruschel J., Flynn K.C., Laskowski C.J., Umlauf M., et al., Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury, Science, 2011, 331, 928–931 http://dx.doi.org/10.1126/science.120114810.1126/science.1201148Search in Google Scholar PubMed PubMed Central

[52] Sengottuvel V., Leibinger M., Pfreimer M., Andreadaki A., Fischer D., Taxol facilitates axon regeneration in the mature CNS, J. Neurosci., 2011, 31, 2688–2699 http://dx.doi.org/10.1523/JNEUROSCI.4885-10.201110.1523/JNEUROSCI.4885-10.2011Search in Google Scholar PubMed PubMed Central

[53] Bhalala O.G., Srikanth M., Kessler J.A., The emerging roles of microRNAs in CNS injuries, Nat. Rev. Neurol., 2013, 9, 328–339 http://dx.doi.org/10.1038/nrneurol.2013.6710.1038/nrneurol.2013.67Search in Google Scholar PubMed PubMed Central

[54] Motti D., Bixby J.L., Lemmon V.P., MicroRNAs and neuronal development, Semin. Fetal Neonatal Med., 2012, 17, 347–352 http://dx.doi.org/10.1016/j.siny.2012.07.00810.1016/j.siny.2012.07.008Search in Google Scholar PubMed PubMed Central

[55] Saba R., Schratt G.M., MicroRNAs in neuronal development, function and dysfunction, Brain Res., 2010, 1338, 3–13 http://dx.doi.org/10.1016/j.brainres.2010.03.10710.1016/j.brainres.2010.03.107Search in Google Scholar PubMed

[56] Baudet M.L., Zivraj K.H., Abreu-Goodger C., Muldal A., Armisen J., Blenkiron C., et al., miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones, Nat. Neurosci., 2012, 15, 29–38 http://dx.doi.org/10.1038/nn.297910.1038/nn.2979Search in Google Scholar PubMed PubMed Central

[57] Zou Y., Chiu H., Domenger D., Chuang C.F., Chang C., The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrinmediated axon attraction, Sci. Signal., 2012, 5, ra43 http://dx.doi.org/10.1126/scisignal.200243710.1126/scisignal.2002437Search in Google Scholar PubMed PubMed Central

[58] Zou Y., Chiu H., Zinovyeva A., Ambros V., Chuang C.F., Chang C., Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers, Science, 2013, 340, 372–376 http://dx.doi.org/10.1126/science.123132110.1126/science.1231321Search in Google Scholar PubMed PubMed Central

[59] Dajas-Bailador F., Bonev B., Garcez P., Stanley P., Guillemot F., Papalopulu N., microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons, Nat. Neurosci., 2012, Epub ahead of print, doi:10.1038/nn.3082 10.1038/nn.3082Search in Google Scholar PubMed

[60] Franke K., Otto W., Johannes S., Baumgart J., Nitsch R., Schumacher S., miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling, EMBO J., 2012, 31, 2908–2921 http://dx.doi.org/10.1038/emboj.2012.13010.1038/emboj.2012.130Search in Google Scholar PubMed PubMed Central

[61] Yu Y.M., Gibbs K.M., Davila J., Campbell N., Sung S., Todorova T.I., et al., MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish, Eur. J. Neurosci., 2011, 33, 1587–1597 http://dx.doi.org/10.1111/j.1460-9568.2011.07643.x10.1111/j.1460-9568.2011.07643.xSearch in Google Scholar PubMed PubMed Central

[62] Liu C.M., Wang R.Y., Saijilafu, Jiao Z.X., Zhang B.Y., Zhou F.Q., MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration, Genes Dev., 2013, 27, 1473–1483 http://dx.doi.org/10.1101/gad.209619.11210.1101/gad.209619.112Search in Google Scholar PubMed PubMed Central

[63] Strickland I.T., Richards L., Holmes F.E., Wynick D., Uney J.B., Wong L.F., Axotomy-induced miR-21 promotes axon growth in adult dorsal root ganglion neurons, PLoS One, 2011, 6, e23423 http://dx.doi.org/10.1371/journal.pone.002342310.1371/journal.pone.0023423Search in Google Scholar PubMed PubMed Central

[64] Zhou S., Shen D., Wang Y., Gong L., Tang X., Yu B., et al., microRNA-222 targeting PTEN promotes neurite outgrowth from adult dorsal root ganglion neurons following sciatic nerve transection, PLoS One, 2012, 7, e44768 http://dx.doi.org/10.1371/journal.pone.004476810.1371/journal.pone.0044768Search in Google Scholar PubMed PubMed Central

[65] Gaub P., Tedeschi A., Puttagunta R., Nguyen T., Schmandke A., Di Giovanni S., HDAC inhibition promotes neuronal outgrowth and counteracts growth cone collapse through CBP/p300 and P/CAFdependent p53 acetylation, Cell Death Differ., 2010, 17, 1392–1408 http://dx.doi.org/10.1038/cdd.2009.21610.1038/cdd.2009.216Search in Google Scholar PubMed

[66] Gaub P., Joshi Y., Wuttke A., Naumann U., Schnichels S., Heiduschka P., et al., The histone acetyltransferase p300 promotes intrinsic axonal regeneration, Brain, 2011, 134, 2134–2148 http://dx.doi.org/10.1093/brain/awr14210.1093/brain/awr142Search in Google Scholar PubMed

[67] Hershko A., Ciechanover A., The ubiquitin system, Annu. Rev. Biochem., 1998, 67, 425–479 http://dx.doi.org/10.1146/annurev.biochem.67.1.42510.1146/annurev.biochem.67.1.425Search in Google Scholar PubMed

[68] Deshaies R.J., Joazeiro C.A., RING domain E3 ubiquitin ligases, Annu. Rev. Biochem., 2009, 78, 399–434 http://dx.doi.org/10.1146/annurev.biochem.78.101807.09380910.1146/annurev.biochem.78.101807.093809Search in Google Scholar PubMed

[69] Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G., et al., A proteomics approach to understanding protein ubiquitination, Nat. Biotechnol., 2003, 21, 921–926 http://dx.doi.org/10.1038/nbt84910.1038/nbt849Search in Google Scholar PubMed

[70] Lim K.L., Lim G.G., K63-linked ubiquitination and neurodegeneration, Neurobiol. Dis., 2011, 43, 9–16 http://dx.doi.org/10.1016/j.nbd.2010.08.00110.1016/j.nbd.2010.08.001Search in Google Scholar PubMed

[71] Ikeda F., Dikic I., Atypical ubiquitin chains: new molecular signals. ‘Protein Modifications: Beyond the Usual Suspects’ review series, EMBO Rep., 2008, 9, 536–542 http://dx.doi.org/10.1038/embor.2008.9310.1038/embor.2008.93Search in Google Scholar PubMed PubMed Central

[72] Welchman R.L., Gordon C., Mayer R.J., Ubiquitin and ubiquitin-like proteins as multifunctional signals, Nat. Rev. Mol. Cell Biol., 2005, 6, 599–609 http://dx.doi.org/10.1038/nrm170010.1038/nrm1700Search in Google Scholar PubMed

[73] Komander D., Clague M.J., Urbe S., Breaking the chains: structure and function of the deubiquitinases, Nat. Rev. Mol. Cell Biol., 2009, 10, 550–563 http://dx.doi.org/10.1038/nrm273110.1038/nrm2731Search in Google Scholar PubMed

[74] Yi J.J., Ehlers M.D., Emerging roles for ubiquitin and protein degradation in neuronal function, Pharmacol. Rev., 2007, 59, 14–39 http://dx.doi.org/10.1124/pr.59.1.410.1124/pr.59.1.4Search in Google Scholar PubMed

[75] Kawabe H., Brose N., The role of ubiquitylation in nerve cell development, Nat. Rev. Neurosci., 2011, 12, 251–268 http://dx.doi.org/10.1038/nrn300910.1038/nrn3009Search in Google Scholar PubMed

[76] Stegmuller J., Bonni A., Destroy to create: E3 ubiquitin ligases in neurogenesis, F1000 Biol. Rep., 2010, 2, 38 10.3410/B2-38Search in Google Scholar PubMed PubMed Central

[77] Ciechanover A., Brundin P., The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg, Neuron, 2003, 40, 427–446 http://dx.doi.org/10.1016/S0896-6273(03)00606-810.1016/S0896-6273(03)00606-8Search in Google Scholar PubMed

[78] Campbell D.S., Holt C.E., Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation, Neuron, 2001, 32, 1013–1026 http://dx.doi.org/10.1016/S0896-6273(01)00551-710.1016/S0896-6273(01)00551-7Search in Google Scholar

[79] Kim T.H., Lee H.K., Seo I.A., Bae H.R., Suh D.J., Wu J., et al., Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron, J. Neurochem., 2005, 95, 1–8 http://dx.doi.org/10.1111/j.1471-4159.2005.03314.x10.1111/j.1471-4159.2005.03314.xSearch in Google Scholar PubMed PubMed Central

[80] Li H., Kulkarni G., Wadsworth W.G., RPM-1, a Caenorhabditis elegans protein that functions in presynaptic differentiation, negatively regulates axon outgrowth by controlling SAX-3/robo and UNC-5/UNC5 activity, J. Neurosci., 2008, 28, 3595–3603 http://dx.doi.org/10.1523/JNEUROSCI.5536-07.200810.1523/JNEUROSCI.5536-07.2008Search in Google Scholar PubMed PubMed Central

[81] Hammarlund M., Nix P., Hauth L., Jorgensen E.M., Bastiani M., Axon regeneration requires a conserved MAP kinase pathway, Science, 2009, 323, 802–806 http://dx.doi.org/10.1126/science.116552710.1126/science.1165527Search in Google Scholar PubMed PubMed Central

[82] Lewcock J.W., Genoud N., Lettieri K., Pfaff S.L., The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics, Neuron, 2007, 56, 604–620 http://dx.doi.org/10.1016/j.neuron.2007.09.00910.1016/j.neuron.2007.09.009Search in Google Scholar PubMed

[83] Saiga T., Fukuda T., Matsumoto M., Tada H., Okano H.J., Okano H., et al., Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development, Mol. Cell. Biol., 2009, 29, 3529–3543 http://dx.doi.org/10.1128/MCB.00364-0910.1128/MCB.00364-09Search in Google Scholar PubMed PubMed Central

[84] Tursun B., Schluter A., Peters M.A., Viehweger B., Ostendorff H.P., Soosairajah J., et al., The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones, Genes Dev., 2005, 19, 2307–2319 http://dx.doi.org/10.1101/gad.134060510.1101/gad.1340605Search in Google Scholar PubMed PubMed Central

[85] Cheng P.L., Lu H., Shelly M., Gao H., Poo M.M., Phosphorylation of E3 ligase Smurf1 switches its substrate preference in support of axon development, Neuron, 2011, 69, 231–243 http://dx.doi.org/10.1016/j.neuron.2010.12.02110.1016/j.neuron.2010.12.021Search in Google Scholar PubMed

[86] Yuasa-Kawada J., Kinoshita-Kawada M., Wu G., Rao Y., Wu J.Y., Midline crossing and Slit responsiveness of commissural axons require USP33, Nat. Neurosci., 2009, 12, 1087–1089 http://dx.doi.org/10.1038/nn.238210.1038/nn.2382Search in Google Scholar PubMed PubMed Central

[87] Peters J.M., The anaphase promoting complex/cyclosome: a machine designed to destroy, Nat. Rev. Mol. Cell Biol., 2006, 7, 644–656 http://dx.doi.org/10.1038/nrm198810.1038/nrm1988Search in Google Scholar PubMed

[88] Harper J.W., Burton J.L., Solomon M.J., The anaphase-promoting complex: it’s not just for mitosis any more, Genes Dev., 2002, 16, 2179–2206 http://dx.doi.org/10.1101/gad.101310210.1101/gad.1013102Search in Google Scholar PubMed

[89] Burton J.L., Solomon M.J., D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p, Genes Dev., 2001, 15, 2381–2395 http://dx.doi.org/10.1101/gad.91790110.1101/gad.917901Search in Google Scholar PubMed PubMed Central

[90] Pfleger C.M., Kirschner M.W., The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1, Genes Dev., 2000, 14, 655–665 10.1101/gad.14.6.655Search in Google Scholar

[91] Gieffers C., Peters B.H., Kramer E.R., Dotti C.G., Peters J.M., Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons, Proc. Natl. Acad. Sci. USA, 1999, 96, 11317–11322 http://dx.doi.org/10.1073/pnas.96.20.1131710.1073/pnas.96.20.11317Search in Google Scholar PubMed PubMed Central

[92] Konishi Y., Stegmuller J., Matsuda T., Bonni S., Bonni A., Cdh1-APC controls axonal growth and patterning in the mammalian brain, Science, 2004, 303, 1026–1030 http://dx.doi.org/10.1126/science.109371210.1126/science.1093712Search in Google Scholar PubMed

[93] Kim A.H., Puram S.V., Bilimoria P.M., Ikeuchi Y., Keough S., Wong M., et al., A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons, Cell, 2009, 136, 322–336 http://dx.doi.org/10.1016/j.cell.2008.11.05010.1016/j.cell.2008.11.050Search in Google Scholar PubMed PubMed Central

[94] Yang Y., Kim A.H., Yamada T., Wu B., Bilimoria P.M., Ikeuchi Y., et al., A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation, Science, 2009, 326, 575–578 http://dx.doi.org/10.1126/science.117708710.1126/science.1177087Search in Google Scholar PubMed PubMed Central

[95] Puram S.V., Kim A.H., Ikeuchi Y., Wilson-Grady J.T., Merdes A., Gygi S.P., et al., A CaMKIIbeta signaling pathway at the centrosome regulates dendrite patterning in the brain, Nat. Neurosci., 2011, 14, 973–983 http://dx.doi.org/10.1038/nn.285710.1038/nn.2857Search in Google Scholar PubMed PubMed Central

[96] Yang Y., Kim A.H., Bonni A., The dynamic ubiquitin ligase duo: Cdh1-APC and Cdc20-APC regulate neuronal morphogenesis and connectivity, Curr. Opin. Neurobiol., 2010, 20, 92–99 http://dx.doi.org/10.1016/j.conb.2009.12.00410.1016/j.conb.2009.12.004Search in Google Scholar PubMed PubMed Central

[97] Stegmuller J., Konishi Y., Huynh M.A., Yuan Z., Dibacco S., Bonni A., Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN, Neuron, 2006, 50, 389–400 http://dx.doi.org/10.1016/j.neuron.2006.03.03410.1016/j.neuron.2006.03.034Search in Google Scholar PubMed

[98] Stroschein S.L., Bonni S., Wrana J.L., Luo K., Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN, Genes Dev., 2001, 15, 2822–2836 10.1101/gad.912901Search in Google Scholar PubMed PubMed Central

[99] Wan Y., Liu X., Kirschner M.W., The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction, Mol. Cell, 2001, 8, 1027–1039 http://dx.doi.org/10.1016/S1097-2765(01)00382-310.1016/S1097-2765(01)00382-3Search in Google Scholar

[100] Liu X., Sun Y., Weinberg R.A., Lodish H.F., Ski/Sno and TGF-beta signaling, Cytokine Growth Factor Rev., 2001, 12, 1–8 http://dx.doi.org/10.1016/S1359-6101(00)00031-910.1016/S1359-6101(00)00031-9Search in Google Scholar PubMed

[101] Ikeuchi Y., Stegmuller J., Netherton S., Huynh M.A., Masu M., Frank D., et al., A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain, J. Neurosci., 2009, 29, 4312–4321 http://dx.doi.org/10.1523/JNEUROSCI.0126-09.200910.1523/JNEUROSCI.0126-09.2009Search in Google Scholar PubMed PubMed Central

[102] Bonni S., Wang H.R., Causing C.G., Kavsak P., Stroschein S.L., Luo K., et al., TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation, Nat. Cell Biol., 2001, 3, 587–595 http://dx.doi.org/10.1038/3507856210.1038/35078562Search in Google Scholar PubMed

[103] Stegmuller J., Huynh M.A., Yuan Z., Konishi Y., Bonni A., TGFbeta-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis, J. Neurosci., 2008, 28, 1961–1969 http://dx.doi.org/10.1523/JNEUROSCI.3061-07.200810.1523/JNEUROSCI.3061-07.2008Search in Google Scholar PubMed PubMed Central

[104] Lasorella A., Stegmuller J., Guardavaccaro D., Liu G., Carro M.S., Rothschild G., et al., Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth, Nature, 2006, 442, 471–474 http://dx.doi.org/10.1038/nature0489510.1038/nature04895Search in Google Scholar PubMed

[105] Zachariae W., Schwab M., Nasmyth K., Seufert W., Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex, Science, 1998, 282, 1721–1724 http://dx.doi.org/10.1126/science.282.5394.172110.1126/science.282.5394.1721Search in Google Scholar PubMed

[106] Huynh M.A., Stegmuller J., Litterman N., Bonni A., Regulation of Cdh1-APC function in axon growth by Cdh1 phosphorylation, J. Neurosci., 2009, 29, 4322–4327 http://dx.doi.org/10.1523/JNEUROSCI.5329-08.200910.1523/JNEUROSCI.5329-08.2009Search in Google Scholar PubMed PubMed Central

[107] Su S.C., Tsai L.H., Cyclin-dependent kinases in brain development and disease, Annu. Rev. Cell Dev. Biology, 2011, 27, 465–491 http://dx.doi.org/10.1146/annurev-cellbio-092910-15402310.1146/annurev-cellbio-092910-154023Search in Google Scholar PubMed

[108] Bermel C., Tonges L., Planchamp V., Gillardon F., Weishaupt J.H., Dietz G.P., et al., Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells, Mol. Cell. Neurosci., 2009, 42, 427–437 http://dx.doi.org/10.1016/j.mcn.2009.09.00510.1016/j.mcn.2009.09.005Search in Google Scholar PubMed

[109] Kannan M., Lee S.J., Schwedhelm-Domeyer N., Stegmuller J., The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth, Development, 2012, 139, 3600–3612 http://dx.doi.org/10.1242/dev.08178610.1242/dev.081786Search in Google Scholar PubMed

[110] Wang H.R., Zhang Y., Ozdamar B., Ogunjimi A.A., Alexandrova E., Thomsen G.H., et al., Regulation of cell polarity and protrusion formation by targeting RhoA for degradation, Science, 2003, 302, 1775–1779 http://dx.doi.org/10.1126/science.109077210.1126/science.1090772Search in Google Scholar PubMed

[111] Kannan M., Lee S.J., Schwedhelm-Domeyer N., Nakazawa T., Stegmuller J., p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation, PLoS One, 2012, 7, e50735 http://dx.doi.org/10.1371/journal.pone.005073510.1371/journal.pone.0050735Search in Google Scholar PubMed PubMed Central

[112] Nakazawa T., Watabe A.M., Tezuka T., Yoshida Y., Yokoyama K., Umemori H., et al., p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling, Mol. Biol. Cell, 2003, 14, 2921–2934 10.1091/mbc.e02-09-0623Search in Google Scholar PubMed PubMed Central

[113] Yu P., Zhang Y.P., Shields L.B., Zheng Y., Hu X., Hill R., et al., Inhibitor of DNA binding 2 promotes sensory axonal growth after SCI, Exp. Neurol., 2011, 231, 38–44 http://dx.doi.org/10.1016/j.expneurol.2011.05.01310.1016/j.expneurol.2011.05.013Search in Google Scholar PubMed

[114] Do J.L., Bonni A., Tuszynski M.H., SnoN facilitates axonal regeneration after spinal cord injury, PLoS ONE, 2013, 8, e71906 http://dx.doi.org/10.1371/journal.pone.007190610.1371/journal.pone.0071906Search in Google Scholar PubMed PubMed Central