Skip to main content
SpringerLink
Log in

Role of L1CAM for axon sprouting and branching

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The central nervous system (CNS) has been traditionally considered as an organ that fails to regenerate in response to injury. Indeed, the lesioned CNS faces a number of obstacles during regeneration, including an overall non-permissive environment for axonal regeneration. However, research during the last few decades has identified axon sprouting as an anatomical correlate for the regenerative capability of the CNS to establish new connections. The immunoglobulin superfamily member L1CAM has been shown to promote the capability of neurons for regenerative axon sprouting and to improve behavioral outcomes after CNS injury. Here, we discuss the cell-autonomous role of L1CAM for axon sprouting in experimental rodent injury models and highlight the molecular interactions of L1CAM with ankyrins, ezrin-radixin-moesin proteins and the Sema3A/Neuropilin ligand-receptor complex in the context of axonal branching.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Akopians A, Runyan SA, Phelps PE (2003) Expression of L1 decreases during postnatal development of rat spinal cord. J Comp Neurol 467:375–388

    PubMed  CAS  Google Scholar 

  • Anderson RB, Turner KN, Nikonenko AG, Hemperly J, Schachner M, Young HM (2006) The cell adhesion molecule L1 is required for chain migration of neural crest cells in the developing mouse gut. Gastroenterology 130:1221–1232

    PubMed  CAS  Google Scholar 

  • Antoine-Bertrand J, Ghogha A, Luangrath V, Bedford FK, Lamarche-Vane N (2011) The activation of ezrin-radixin-moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1-induced axon outgrowth. Mol Biol Cell 22:3734–3746

    PubMed  CAS  Google Scholar 

  • Aubert I, Ridet J-L, Schachner M, Rougon G, Gage FH (1998) Expression of L1 and PSA during sprouting and regeneration in the adult hippocampal formation. J Comp Neurol 399:1–19

    PubMed  CAS  Google Scholar 

  • Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME (2004) The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 7:269–277

    PubMed  CAS  Google Scholar 

  • Barry J, Gu Y, Gu C (2010) Polarized targeting of L1-CAM regulates axonal and dendritic bundling in vitro. Eur J Neurosci 32:1618–1631

    PubMed  Google Scholar 

  • Bechara A, Nawabi H, Moret F, Yaron A, Weaver E, Bozon M, Abouzid K, Guan J-L, Tessier-Lavigne M, Lemmon V, Castellani V (2008) FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse. EMBO J 27:1549–1562

    PubMed  CAS  Google Scholar 

  • Bennett V, Chen L (2001) Ankyrins and cellular targeting of diverse membrane proteins to physiological sites. Curr Opin Cell Biol 13:61–67

    PubMed  CAS  Google Scholar 

  • Bennett V, Lambert S (1999) Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels. J Neurocytol 28:303–318

    PubMed  CAS  Google Scholar 

  • Bernreuther C, Dihné M, Johann V, Schiefer J, Cui Y, Hargus G, Schmid JS, Xu J, Kosinski CM, Schachner M (2006) Neural cell adhesion molecule L1-transfected embryonic stem cells promote functional recovery after excitotoxic lesion of the mouse striatum. J Neurosci 26:11532–11539

    PubMed  CAS  Google Scholar 

  • Boiko T, Vakulenko M, Ewers H, Yap CC, Norden C, Winckler B (2007) Ankyrin-dependent and -independent mechanisms orchestrate axonal compartmentalization of L1 family members neurofascin and L1/neuronal-glia cell adhesion molecule. J Neurosci 27:590–603

    PubMed  CAS  Google Scholar 

  • Buhusi M, Schlatter MC, Demyanenko GP, Thresher R, Maness PF (2008) L1 interaction with ankyrin regulates mediolateral topography in the retinocollicular projection. J Neurosci 28:177–188

    PubMed  CAS  Google Scholar 

  • Castellani V, Chedotal A, Schachner M, Faivre-Sarrailh C, Rougon G (2000) Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance. Neuron 27:237–249

    PubMed  CAS  Google Scholar 

  • Castellani V, De Angelis E, Kenwrick S, Rougon G (2002) Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A. EMBO J 21:6348–6357

    PubMed  CAS  Google Scholar 

  • Castellani V, Falk J, Rougon G (2004) Semaphorin3A-induced receptor endocytosis during axon guidance responses is mediated by L1 CAM. Mol Cell Neurosci 26:89–100

    PubMed  CAS  Google Scholar 

  • Chang S, Rathjen FG, Raper JA (1987) Extension of neurites on axons is impaired by antibodies against specific neural cell surface glycoproteins. J Cell Biol 104:355–362

    PubMed  CAS  Google Scholar 

  • Cheng L, Lemmon V (2004) Pathological missense mutations of neural cell adhesion molecule L1 affect neurite outgrowth and branching on an L1 substrate. Mol Cell Neurosci 27:522–530

    PubMed  CAS  Google Scholar 

  • Cheng L, Itoh K, Lemmon V (2005) L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region. J Neurosci 25:395–403

    PubMed  CAS  Google Scholar 

  • Cohen NR, Taylor JSH, Scott LB, Guillery RW, Soriano P, Furley AJW (1998) Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol 8:26–33

    PubMed  CAS  Google Scholar 

  • Courtine G, Song B, Roy RR, Zhong H, Herrmann JE, Ao Y, Qi J, Edgerton VR, Sofroniew MV (2008) Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med 14:69–74

    PubMed  CAS  Google Scholar 

  • Cui Y-F, Hargus G, Xu J-C, Schmid JS, Shen Y-Q, Glatzel M, Schachner M, Bernreuther C (2009) Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery in Parkinsonian mice. Brain 133:189–204

    PubMed  Google Scholar 

  • Cui Y-F, Xu J-C, Hargus G, Jakovcevski I, Schachner M, Bernreuther C (2011) Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice. PLoS One 6:e17126

    PubMed  CAS  Google Scholar 

  • Dahlin-Huppe K, Berglund EO, Ranscht B, Stallcup WB (1997) Mutational analysis of the L1 neuronal cell adhesion molecule identifies membrane-proximal amino acids of the cytoplasmic domain that are required for cytoskeletal anchorage. Mol Cell Neurosci 9:144–156

    PubMed  CAS  Google Scholar 

  • Dahme M, Bartsch U, Martini R, Anliker B, Schachner M, Mantei N (1997) Disruption of the mouse L1 gene leads to malformations of the nervous system. Nat Genet 17:346–349

    PubMed  CAS  Google Scholar 

  • Davis JQ, Bennett V (1994) Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. J Biol Chem 269:27163–27166

    PubMed  CAS  Google Scholar 

  • Davis JQ, McLaughlin T, Bennett V (1993) Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain. J Cell Biol 121:121–133

    PubMed  CAS  Google Scholar 

  • Deller T, Nitsch R, Frotscher M (1996) Layer-specific sprouting of commissural fibres to the rat fascia dentata after unilateral entorhinal cortex lesion: a Phaseolus vulgaris leucoagglutinin tracing study. Neuroscience 71:651–660

    PubMed  CAS  Google Scholar 

  • Deller T, Haas C, Freiman T, Phinney A, Jucker M, Frotscher M (2006) Lesion-induced axonal sprouting in the central nervous system. Adv Exp Med Biol 557:101–121

    PubMed  CAS  Google Scholar 

  • Demyanenko GP, Tsai AY, Maness PF (1999) Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice. J Neurosci 19:4907–4920

    PubMed  CAS  Google Scholar 

  • Dequidt C, Danglot L, Alberts P, Galli T, Choquet D, Thoumine O (2007) Fast turnover of L1 adhesions in neuronal growth cones involving both surface diffusion and exo/endocytosis of L1 molecules. Mol Biol Cell 18:3131–3143

    PubMed  CAS  Google Scholar 

  • Deumens R, Lübbers M, Jaken RJP, Meijs MFL, Thurlings RM, Honig WMM, Schachner M, Brook GA, Joosten EAJ (2007) Mice lacking L1 have reduced CGRP fibre in-growth into spinal transection lesions. Neurosci Lett 420:277–281

    PubMed  CAS  Google Scholar 

  • Dickson TC, Mintz CD, Benson DL, Salton SRJ (2002) Functional binding interaction identified between the axonal CAM L1 and members of the ERM family. J Cell Biol 157:1105–1112

    PubMed  CAS  Google Scholar 

  • Diez-Revuelta N, Velasco S, Andre S, Kaltner H, Kübler D, Gabius H-J, Abad-Rodriguez J (2010) Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution. J Cell Sci 123:671–681

    PubMed  CAS  Google Scholar 

  • Dimou L, Schnell L, Montani L, Duncan C, Simonen M, Schneider R, Liebscher T, Gullo M, Schwab ME (2006) Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration. J Neurosci 26:5591–5603

    PubMed  CAS  Google Scholar 

  • Dubreuil RR, MacVicar G, Dissanayake S, Liu C, Homer D, Hortsch M (1996) Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites. J Cell Biol 133:647–655

    PubMed  CAS  Google Scholar 

  • Dzhashiashvili Y, Zhang Y, Galinska J, Lam I, Grumet M, Salzer JL (2007) Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms. J Cell Biol 177:857–870

    PubMed  CAS  Google Scholar 

  • Faissner A, Kruse J, Nieke J, Schachner M (1984) Expression of neural cell adhesion molecule L1 during development, in neurological mutants and in the peripheral nervous system. Brain Res 317:69–82

    PubMed  CAS  Google Scholar 

  • Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 11:276–287

    PubMed  CAS  Google Scholar 

  • Fransen E, Vits L, Camp GV, Willems PJ (1996) The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule. Am J Med Genet 64:73–77

    PubMed  CAS  Google Scholar 

  • Fransen E, D'Hooge R, Van Camp G, Verhoye M, Sijbers J, Reyniers E, Soriano P, Kamiguchi H, Willemsen R, Koekkoek SKE, De Zeeuw CI, De Deyn PP, Van der Linden A, Lemmon V, Kooy RF, Willems PJ (1998) L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum Mol Genet 7:999–1009

    PubMed  CAS  Google Scholar 

  • Friedlander DR, Milev P, Karthikeyan L, Margolis RK, Margolis RU, Grumet M (1994) The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. J Cell Biol 125:669–680

    PubMed  CAS  Google Scholar 

  • Gallo G (2008) Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K. Dev Neurobiol 68:926–933

    PubMed  CAS  Google Scholar 

  • Garver TD, Ren Q, Tuvia S, Bennett V (1997) Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin. J Cell Biol 137:703–714

    PubMed  CAS  Google Scholar 

  • Giger RJ, Hollis ER, Tuszynski MH (2011) Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol 2:a001867

    Google Scholar 

  • Gil OD, Sakurai T, Bradley AE, Fink MY, Cassella MR, Kuo JA, Felsenfeld DP (2003) Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface. J Cell Biol 162:719–730

    PubMed  CAS  Google Scholar 

  • Godenschwege TA, Kristiansen LV, Uthaman SB, Hortsch M, Murphey RK (2006) A conserved role for Drosophila neuroglian and human L1-CAM in central-synapse formation. Curr Biol 16:12–23

    PubMed  CAS  Google Scholar 

  • Goldshmit Y, Lythgo N, Galea MP, Turnley AM (2008) Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. J Neurotrauma 25:449–465

    PubMed  Google Scholar 

  • Grumet M, Mauro V, Burgoon MP, Edelman GM, Cunningham BA (1991) Structure of a new nervous system glycoprotein, Nr-CAM, and its relationship to subgroups of neural cell adhesion molecules. J Cell Biol 113:1399–1412

    PubMed  CAS  Google Scholar 

  • Guan H, Maness PF (2010) Perisomatic GABAergic innervation in prefrontal cortex is regulated by ankyrin interaction with the L1 cell adhesion molecule. Cereb Cortex 20:2684–2693

    PubMed  Google Scholar 

  • Haas MA, Vickers JC, Dickson TC (2004) Binding partners L1 cell adhesion molecule and the ezrin-radixin-moesin (ERM) proteins are involved in development and the regenerative response to injury of hippocampal and cortical neurons. Eur J Neurosci 20:1436–1444

    PubMed  Google Scholar 

  • Haspel J, Grumet M (2003) The L1CAM extracellular region: a multi-domain protein with modular and cooperative binding modes. Front Biosci 8:1210–1225

    Google Scholar 

  • Herron L, Hill M, Davey F, Gunn-Moore F (2009) The intracellular interactions of the L1 family of cell adhesion molecules. Biochem J 1:519–531

    Google Scholar 

  • Hoffman EJ, Mintz CD, Wang S, McNickle DG, Salton SRJ, Benson DL (2008) Effects of ethanol on axon outgrowth and branching in developing rat cortical neurons. Neuroscience 157:556–565

    PubMed  CAS  Google Scholar 

  • Holm J, Hillenbrand R, Steuber V, Bartsch U, Moos M, Lübbert H, Montag D, Schachner M (1996) Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules. Eur J Neurosci 8:1613–1629

    PubMed  CAS  Google Scholar 

  • Hortsch M, O'Shea KS, Zhao G, Kim F, Vallejo Y, Dubreuil RR (1998) A conserved role for L1 as a transmembrane link between neuronal adhesion and membrane cytoskeleton assembly. Cell Commun Adhes 5:61–73

    CAS  Google Scholar 

  • Hortsch M, Nagaraj K, Godenschwege T (2009) The interaction between L1-type proteins and ankyrins—a master switch for L1-type CAM function. Cell Mol Biol Lett 14:57–69

    PubMed  CAS  Google Scholar 

  • Hoschouer EL, Yin FQ, Jakeman LB (2009) L1 cell adhesion molecule is essential for the maintenance of hyperalgesia after spinal cord injury. Exp Neurol 216:22–34

    PubMed  CAS  Google Scholar 

  • Huang ZJ (2006) Subcellular organization of GABAergic synapses: role of ankyrins and L1 cell adhesion molecules. Nat Neurosci 9:163–166

    PubMed  CAS  Google Scholar 

  • Itoh K, Cheng L, Kamei Y, Fushiki S, Kamiguchi H, Gutwein P, Stoeck A, Arnold B, Altevogt P, Lemmon V (2004) Brain development in mice lacking L1-L1 homophilic adhesion. J Cell Biol 165:145–154

    PubMed  CAS  Google Scholar 

  • Jaerve A, Schiwy N, Schmitz C, Mueller HW (2011) Differential effect of aging on axon sprouting and regenerative growth in spinal cord injury. Exp Neurol 231:284–294

    PubMed  CAS  Google Scholar 

  • Jakeman LB, Chen Y, Lucin KM, McTigue DM (2006) Mice lacking L1 cell adhesion molecule have deficits in locomotion and exhibit enhanced corticospinal tract sprouting following mild contusion injury to the spinal cord. Eur J Neurosci 23:1997–2011

    PubMed  Google Scholar 

  • Jouet M, Rosenthal A, MacFarlane J, Kenwrick S, Donnai D (1993) A missense mutation confirms the L1 defect in X-linked hydrocephalus (HSAS). Nat Genet 4:331

    PubMed  CAS  Google Scholar 

  • Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K, Kenwrick S (1994) X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet 7:402–407

    PubMed  CAS  Google Scholar 

  • Jouet M, Moncla A, Paterson J, McKeown C, Fryer A, Carpenter N, Holmberg E, Wadelius C, Kenwrick S (1995) New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome. Am J Hum Genet 56:1304–1314

    PubMed  CAS  Google Scholar 

  • Jucker M, D'Amat F, Mondadori C, Mohajeri H, Magyar J, Bartsch U, Schachner M (1996) Expression of the neural adhesion molecule L1 in the deafferented dentate gyrus. Neuroscience 75:703–715

    PubMed  CAS  Google Scholar 

  • Kallunki P, Edelman GM, Jones FS (1997) Tissue-specific expression of the L1 cell adhesion molecule is modulated by the neural restrictive silencer element. J Cell Biol 138:1343–1354

    PubMed  CAS  Google Scholar 

  • Kamiguchi H, Lemmon V (2000) Recycling of the cell adhesion molecule L1 in axonal growth cones. J Neurosci 20:3676–3686

    PubMed  CAS  Google Scholar 

  • Kamiguchi H, Yoshihara F (2001) The role of endocytic L1 trafficking in polarized adhesion and migration of nerve growth cones. J Neurosci 21:9194–9203

    PubMed  CAS  Google Scholar 

  • Kamiguchi H, Long KE, Pendergast M, Schaefer AW, Rapoport I, Kirchhausen T, Lemmon V (1998) The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway. J Neurosci 18:5311–5321

    PubMed  CAS  Google Scholar 

  • Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H, Yamasaki M (2006) Molecular mechanisms and neuroimaging criteria for severe L1 syndrome with X-linked hydrocephalus. J Neurosurg 105:403–412

    PubMed  Google Scholar 

  • Kerr BJ, David S (2007) Pain behaviors after spinal cord contusion injury in two commonly used mouse strains. Exp Neurol 206:240–247

    PubMed  Google Scholar 

  • Konya D, Liao W-L, Choi H, Yu D, Woodard MC, Newton KM, King AM, Pamir NM, Black PM, Frontera WR, Sabharwal S, Teng YD (2008) Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity. Regen Med 3:309–327

    PubMed  CAS  Google Scholar 

  • Lasiecka ZM, Winckler B (2011) Mechanisms of polarized membrane trafficking in neurons—focusing in on endosomes. Mol Cell Neurosci 48:278–287

    PubMed  CAS  Google Scholar 

  • Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R (2011) Cell adhesion molecules in gene and cell therapy approaches for nervous system repair. Curr Gene Ther 11:90–100

    PubMed  CAS  Google Scholar 

  • Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B (2010) Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66:663–670

    PubMed  CAS  Google Scholar 

  • Li S, Overman JJ, Katsman D, Kozlov SV, Donnelly CJ, Twiss JL, Giger RJ, Coppola G, Geschwind DH, Carmichael ST (2010) An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke. Nat Neurosci 13:1496–1504

    PubMed  CAS  Google Scholar 

  • Li YL, Wu GZ, Dawe GS, Zeng L, Cui SS, Loers G, Tilling T, Sun L, Schachner M, Xiao ZC (2008) Cell surface sialylation and fucosylation are regulated by L1 via phospholipase Cgamma and cooperate to modulate neurite outgrowth, cell survival and migration. PLoS ONE 3:e3841

    PubMed  Google Scholar 

  • Liljelund P, Ghosh P, Pol AN van den (1994) Expression of the neural axon adhesion molecule L1 in the developing and adult rat brain. J Biol Chem 269:32886–32895

    PubMed  CAS  Google Scholar 

  • Ma M, Wei P, Wei T, Ransohoff RM, Jakeman LB (2004) Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129X1/SvJ) with a diminished inflammatory response. J Comp Neurol 474:469–486

    PubMed  Google Scholar 

  • Malhotra JD, Tsiotra P, Karagogeos D, Hortsch M (1998) Cis-activation of L1-mediated ankyrin recruitment by TAG-1 homophilic cell adhesion. J Biol Chem 273:33354–33359

    PubMed  CAS  Google Scholar 

  • Maness PF, Schachner M (2007) Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat Neurosci 10:19–26

    PubMed  CAS  Google Scholar 

  • Marsick BM, San Miguel-Ruiz JE, Letourneau PC (2012) Activation of ezrin/radixin/moesin mediates attractive growth cone guidance through regulation of growth cone actin and adhesion receptors. J Neurosci 32:282–296

    PubMed  CAS  Google Scholar 

  • Matsumoto-Miyai K, Ninomiya A, Yamasaki H, Tamura H, Nakamura Y, Shiosaka S (2003) NMDA-dependent proteolysis of presynaptic adhesion molecule L1 in the hippocampus by neuropsin. J Neurosci 23:7727–7736

    PubMed  CAS  Google Scholar 

  • Mintz CD, Carcea I, McNickle DG, Dickson TC, Ge Y, Salton SRJ, Benson DL (2008) ERM proteins regulate growth cone responses to Sema3A. J Comp Neurol 510:351–366

    PubMed  CAS  Google Scholar 

  • Montgomery AM, Becker JC, Siu CH, Lemmon VP, Cheresh DA, Pancook JD, Zhao X, Reisfeld RA (1996) Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. J Cell Biol 132:475–485

    PubMed  CAS  Google Scholar 

  • Moon M-s, Gomez TM (2010) Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo. Mol Cell Neurosci 44:118–128

    PubMed  CAS  Google Scholar 

  • Nakamura Y, Tamura H, Horinouchi K, Shiosaka S (2006) Role of neuropsin in formation and maturation of Schaffer-collateral L1cam-immunoreactive synaptic boutons. J Cell Sci 119:1341–1349

    PubMed  CAS  Google Scholar 

  • Nakamura Y, Lee S, Haddox CL, Weaver EJ, Lemmon VP (2010) Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development. J Comp Neurol 518:1113–1132

    PubMed  CAS  Google Scholar 

  • Needham LK, Thelen K, Maness PF (2001) Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions. J Neurosci 21:1490–1500

    PubMed  CAS  Google Scholar 

  • Nishimura K, Yoshihara F, Tojima T, Ooashi N, Yoon W, Mikoshiba K, Bennett V, Kamiguchi H (2003) L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow. J Cell Biol 163:1077–1088

    PubMed  CAS  Google Scholar 

  • Nishimura K, Akiyama H, Komada M, Kamiguchi H (2007) BetaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment. Mol Cell Neurosci 34:422–430

    PubMed  CAS  Google Scholar 

  • Ohyama K, Tan-Takeuchi K, Kutsche M, Schachner M, Uyemura K, Kawamura K (2004) Neural cell adhesion molecule L1 is required for fasciculation and routing of thalamocortical fibres and corticothalamic fibres. Neurosci Res 48:471–475

    PubMed  CAS  Google Scholar 

  • Oleszewski M, Beer S, Katich S, Geiger C, Zeller Y, Rauch U, Altevogt P (1999) Integrin and neurocan binding to L1 involves distinct Ig domains. J Biol Chem 274:24602–24610

    PubMed  CAS  Google Scholar 

  • Omoto S, Ueno M, Mochio S, Takai T, Yamashita T (2010) Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. J Neurosci 30:13045–13052

    PubMed  CAS  Google Scholar 

  • Ooashi N, Kamiguchi H (2009) The cell adhesion molecule L1 controls growth cone navigation via ankyrinB-dependent modulation of cyclic AMP. Neurosci Res 63:224–226

    PubMed  CAS  Google Scholar 

  • Ourednik V, Ourednik J, Xu Y, Zhang Y, Lynch WP, Snyder EY, Schachner M (2009) Cross-talk between stem cells and the dysfunctional brain is facilitated by manipulating the niche: evidence from an adhesion molecule. Stem Cells 27:2846–2856

    PubMed  CAS  Google Scholar 

  • Rathjen FG, Schachner M (1984) Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J 3:1–10

    PubMed  CAS  Google Scholar 

  • Rosenthal A, Jouet M, Kenwrick S (1992) Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nat Genet 2:107–112

    PubMed  CAS  Google Scholar 

  • Runyan SA, Roy R, Zhong H, Phelps PE (2005) L1 CAM expression in the superficial dorsal horn is derived from the dorsal root ganglion. J Comp Neurol 485:267–279

    PubMed  CAS  Google Scholar 

  • Runyan SA, Roy RR, Zhong H, Phelps PE (2007) L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation. Neuroscience 150:959–969

    PubMed  CAS  Google Scholar 

  • Ruppert M, Aigner S, Hubbe M, Yagita H, Altevogt P (1995) The L1 adhesion molecule is a cellular ligand for VLA-5. J Cell Biol 131:1881–1891

    PubMed  CAS  Google Scholar 

  • Saghatelyan AK, Nikonenko AG, Sun M, Rolf B, Putthoff P, Kutsche M, Bartsch U, Dityatev A, Schachner M (2004) Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in juvenile mice deficient in the neural cell adhesion molecule L1. Mol Cell Neurosci 26:191–203

    PubMed  CAS  Google Scholar 

  • Sakurai T, Gil OD, Whittard JD, Gazdoiu M, Joseph T, Wu J, Waksman A, Benson DL, Salton SR, Felsenfeld DP (2008) Interactions between the L1 cell adhesion molecule and ezrin support traction-force generation and can be regulated by tyrosine phosphorylation. J Neurosci Res 86:2602–2614

    PubMed  CAS  Google Scholar 

  • Schaefer AW, Kamei Y, Kamiguchi H, Wong EV, Rapoport I, Kirchhausen T, Beach CM, Landreth G, Lemmon SK, Lemmon V (2002) L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1. J Cell Biol 157:1223–1232

    PubMed  CAS  Google Scholar 

  • Schäfer M, Altevogt P (2010) L1CAM malfunction in the nervous system and human carcinomas. Cell Mol Life Sci 67:2425–2437

    PubMed  Google Scholar 

  • Schäfer MKE, Schmitz B, Diestel S (2010a) L1CAM ubiquitination facilitates its lysosomal degradation. FEBS Lett 584:4475–4480

    PubMed  Google Scholar 

  • Schäfer MKE, Nam Y-C, Moumen A, Keglowich L, Bouché E, Küffner M, Bock HH, Rathjen FG, Raoul C, Frotscher M (2010b) L1 syndrome mutations impair neuronal L1 function at different levels by divergent mechanisms. Neurobiol Dis 40:222–237

    PubMed  Google Scholar 

  • Schlatter MC, Buhusi M, Wright AG, Maness PF (2008) CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane. J Neurochem 104:731–744

    PubMed  CAS  Google Scholar 

  • Scotland P, Zhou D, Benveniste H, Bennett V (1998) Nervous system defects of AnkyrinB (-/-) mice suggest functional overlap between the cell adhesion molecule L1 and 440-kD AnkyrinB in premyelinated axons. J Cell Biol 143:1305–1315

    PubMed  CAS  Google Scholar 

  • Stallcup WB, Beasley L (1985) Involvement of the nerve growth factor-inducible large external glycoprotein (NILE) in neurite fasciculation in primary cultures of rat brain. Proc Natl Acad Sci USA 82:1276–1280

    PubMed  CAS  Google Scholar 

  • Styren SD, Miller PD, Cf L, DeKosky ST (1995) Alternate strategies in lesion-induced reactive synaptogenesis: differetial expression of L1 in two populations of sprouting axons. Exp Neurol 131:165–173

    PubMed  CAS  Google Scholar 

  • Tapanes-Castillo A, Weaver E, Smith R, Kamei Y, Caspary T, Hamilton-Nelson K, Slifer S, Martin E, Bixby J, Lemmon V (2010) A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice. Neurogenetics 11:53–71

    PubMed  CAS  Google Scholar 

  • Triana-Baltzer GB, Liu Z, Berg DK (2006) Pre- and postsynaptic actions of L1-CAM in nicotinic pathways. Mol Cell Neurosci 33:214–226

    PubMed  CAS  Google Scholar 

  • Volkmer H, Hassel B, Wolff JM, Frank R, Rathjen FG (1992) Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily. J Cell Biol 118:149–161

    PubMed  CAS  Google Scholar 

  • Vos YJ, Hofstra RMW (2010) An updated and upgraded L1CAM mutation database. Hum Mutat 31:E1102–E1109

    PubMed  Google Scholar 

  • Weidner N, Ner A, Salimi N, Tuszynski MH (2001) Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc Nat Acad Sci USA 98:3513–3518

    PubMed  CAS  Google Scholar 

  • Whittard JD, Sakurai T, Cassella MR, Gazdoiu M, Felsenfeld DP (2006) MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth. Mol Biol Cell 17:2696–2706

    PubMed  CAS  Google Scholar 

  • Wiencken-Barger AE, Mavity-Hudson J, Bartsch U, Schachner M, Casagrande VA (2004) The role of L1 in axon pathfinding and fasciculation. Cereb Cortex 14:121–131

    PubMed  CAS  Google Scholar 

  • Wolman MA, Regnery AM, Becker T, Becker CG, Halloran MC (2007) Semaphorin3D regulates axon axon interactions by modulating levels of L1 cell adhesion molecule. J Neurosci 27:9653–9663

    PubMed  CAS  Google Scholar 

  • Xu J-C, Bernreuther C, Cui Y-F, Jakovcevski I, Hargus G, Xiao M-F, Schachner M (2011) Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury. J Neurotrauma 28:1921–1937

    PubMed  Google Scholar 

  • Zhang Y, Yeh J, Richardson PM, Bo X (2008) Cell adhesion molecules of the immunoglobulin superfamily in axonal regeneration and neural repair. Restor Neurol Neurosci 26:81–96

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We apologize to everyone whose work was not cited here because of space constraints.

Author information

Authors and Affiliations

  1. Klinik für Anästhesiologie, Universitätsmedizin Mainz, 55131, Mainz, Germany

    Michael K. E. Schäfer

  2. Forschungsschwerpunkt Translationale Neurowissenschaften (FTN), Johannes Gutenberg-Universität Mainz, 55131, Mainz, Germany

    Michael K. E. Schäfer

  3. Zentrum für Molekulare Neurobiologie Hamburg, 20246, Hamburg, Germany

    Michael Frotscher

Authors
  1. Michael K. E. Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Frotscher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael K. E. Schäfer.

Additional information

This work has been supported by the Deutsche Forschungsgemeinschaft (SCHA 1261/4-1 to M.S.). M.F. is Senior Research Professor of the Hertie Foundation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schäfer, M.K.E., Frotscher, M. Role of L1CAM for axon sprouting and branching. Cell Tissue Res 349, 39–48 (2012). https://doi.org/10.1007/s00441-012-1345-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1345-4

Key words

Search

Navigation