neural cell adhesion molecules


Summary: Cell adhesion molecule involved in a diverse range of contact-mediated interactions among neurons, astrocytes, oligodendrocytes, and myotubes. It is widely but transiently expressed in many tissues early in embryogenesis. Four main isoforms exist, including CD56; (CD56 ANTIGEN); but there are many other variants resulting from alternative splicing and post-translational modifications. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, pp115-119)

Top Publications

  1. Suzuki K, Hayashi Y, Nakahara S, Kumazaki H, Prox J, Horiuchi K, et al. Activity-dependent proteolytic cleavage of neuroligin-1. Neuron. 2012;76:410-22 pubmed publisher
    ..Collectively, neuronal activity-dependent proteolytic processing of NLG1 may negatively regulate the remodeling of spines at excitatory synapses. ..
  2. Hansen S, Køhler L, Li S, Kiselyov V, Christensen C, Owczarek S, et al. NCAM-derived peptides function as agonists for the fibroblast growth factor receptor. J Neurochem. 2008;106:2030-41 pubmed publisher
  3. Chocyk A, Dudys D, Przyborowska A, Maćkowiak M, Wędzony K. Impact of maternal separation on neural cell adhesion molecules expression in dopaminergic brain regions of juvenile, adolescent and adult rats. Pharmacol Rep. 2010;62:1218-24 pubmed
    ..b>Neural cell adhesion molecules (NCAM 120, 140, 180 kDa) are known to play an important role in normal brain development and synaptic ..
  4. Gnanapavan S, Grant D, Illes Toth E, Lakdawala N, Keir G, Giovannoni G. Neural cell adhesion molecule--description of a CSF ELISA method and evidence of reduced levels in selected neurological disorders. J Neuroimmunol. 2010;225:118-22 pubmed publisher
    ..Significant reductions were found between controls and multiple sclerosis, Alzheimer's disease and meningitis. ..
  5. Køhler L, Soroka V, Korshunova I, Berezin V, Bock E. A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival. J Neurosci Res. 2010;88:2165-76 pubmed publisher
  6. Ono S, Hane M, Kitajima K, Sato C. Novel regulation of fibroblast growth factor 2 (FGF2)-mediated cell growth by polysialic acid. J Biol Chem. 2012;287:3710-22 pubmed publisher
    ..Taken together, these results suggest that polySia-NCAM might be involved in the regulation of FGF2-FGF receptor signaling through the direct binding of FGF2 in a manner distinct from heparan sulfate. ..
  7. Etherton M, Blaiss C, Powell C, Südhof T. Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci U S A. 2009;106:17998-8003 pubmed publisher
    ..Together, these data indicate that the neurexin-1alpha deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients. ..
  8. Chernyshova Y, Leshchyns ka I, Hsu S, Schachner M, Sytnyk V. The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones. J Neurosci. 2011;31:3522-35 pubmed publisher
    ..Thus, we reveal a novel role for a cell adhesion molecule in that it regulates addition of the new membrane to the cell surface of growth cones in developing neurons. ..
  9. Thompson M, Foley D, Swartzentruber K, Colley K. Sequences at the interface of the fifth immunoglobulin domain and first fibronectin type III repeat of the neural cell adhesion molecule are critical for its polysialylation. J Biol Chem. 2011;286:4525-34 pubmed publisher

More Information


  1. Ishikawa T, Gotoh N, Murayama C, Abe T, Iwashita M, Matsuzaki F, et al. IgSF molecule MDGA1 is involved in radial migration and positioning of a subset of cortical upper-layer neurons. Dev Dyn. 2011;240:96-107 pubmed publisher
    ..These observations indicated that Mdga1 is involved in the migration and positioning of a subset of cortical neurons and suggested that the radial migration of upper-layer neurons might be differentially regulated. ..
  2. Siddiqui T, Craig A. Synaptic organizing complexes. Curr Opin Neurobiol. 2011;21:132-43 pubmed publisher
    ..Together with classical adhesion molecules and controlled by transcriptional cascades, these synaptogenic adhesion complexes and secreted factors organize the molecular composition and thus functional properties of central synapses. ..
  3. Chen Y, Li S, Berezin V, Bock E. The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently. J Neurosci Res. 2010;88:1882-9 pubmed publisher
    ..However, the activation of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor. ..
  4. Nielsen J, Gotfryd K, Li S, Kulahin N, Soroka V, Rasmussen K, et al. Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. J Neurosci. 2009;29:11360-76 pubmed publisher
  5. Dityatev A, Bukalo O, Schachner M. Modulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules. Neuron Glia Biol. 2008;4:197-209 pubmed publisher
  6. Bajor M, Michaluk P, Gulyassy P, Kékesi A, Juhasz G, Kaczmarek L. Synaptic cell adhesion molecule-2 and collapsin response mediator protein-2 are novel members of the matrix metalloproteinase-9 degradome. J Neurochem. 2012;122:775-88 pubmed publisher
  7. Dahlhaus R, Hines R, Eadie B, Kannangara T, Hines D, Brown C, et al. Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus. Hippocampus. 2010;20:305-22 pubmed publisher
  8. Singh J, Kaur G. Transcriptional regulation of PSA-NCAM expression by NMDA receptor activation in RA-differentiated C6 glioma cultures. Brain Res Bull. 2009;79:157-68 pubmed publisher
    ..The results elucidate the possible cellular and molecular mechanisms of regulation of PSA-NCAM expression in astroglial cultures by extracellular signals. ..
  9. Cox E, Brennaman L, Gable K, Hamer R, Glantz L, LaMantia A, et al. Developmental regulation of neural cell adhesion molecule in human prefrontal cortex. Neuroscience. 2009;162:96-105 pubmed publisher
  10. Siddiqui T, Pancaroglu R, Kang Y, Rooyakkers A, Craig A. LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J Neurosci. 2010;30:7495-506 pubmed publisher
    ..Thus, we propose a synaptic code hypothesis suggesting that neurexins are master regulators of the cooperative activities of LRRTMs and neuroligins. ..
  11. Ojo B, Gabbott P, Rezaie P, Corbett N, Medvedev N, Cowley T, et al. An NCAM mimetic, FGL, alters hippocampal cellular morphometry in young adult (4 month-old) rats. Neurochem Res. 2013;38:1208-18 pubmed publisher
    ..These data indicate that FGL has a specific age dependent effect on the hippocampus, differing according to the development and maturity of the CNS. ..
  12. Uemura T, Lee S, Yasumura M, Takeuchi T, Yoshida T, Ra M, et al. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell. 2010;141:1068-79 pubmed publisher
    ..These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1. ..
  13. Bisaz R, Conboy L, Sandi C. Learning under stress: a role for the neural cell adhesion molecule NCAM. Neurobiol Learn Mem. 2009;91:333-42 pubmed publisher
  14. Valentiner U, Muhlenhoff M, Lehmann U, Hildebrandt H, Schumacher U. Expression of the neural cell adhesion molecule and polysialic acid in human neuroblastoma cell lines. Int J Oncol. 2011;39:417-24 pubmed publisher
    ..Together, this indicates that the presence of polySia reduces the adhesiveness of tumour cells and promotes dissemination. ..
  15. Soler Llavina G, Fuccillo M, Ko J, Sudhof T, Malenka R. The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo. Proc Natl Acad Sci U S A. 2011;108:16502-9 pubmed publisher
    ..These results show that neurexin ligands in vivo form a dynamic synaptic cell adhesion network, with compensation between NLs and LRRTMs during early synapse development and functional divergence upon synapse maturation. ..
  16. Køhler L, Christensen C, Rossetti C, Fantin M, Sandi C, Bock E, et al. Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning. Eur J Cell Biol. 2010;89:817-27 pubmed publisher
    ..Thus, dennexins are novel site-specific pharmacological tools for elucidation of the role of NCAM in a variety of biological processes under normal and pathological conditions. ..
  17. Shapiro Reznik M, Jilg A, Lerner H, Earnest D, Zisapel N. Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse scaffold proteins in the biological clock. PLoS ONE. 2012;7:e37894 pubmed publisher
    ..NRXNs gene transcripts may have a role in coupling the circadian clock to diurnal rhythms in excitatory/inhibitory synaptic balance. ..
  18. Secher T, Berezin V, Bock E, Glenthøj B. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats. Behav Brain Res. 2009;199:288-97 pubmed publisher
    ..In conclusion, the results suggest that the neonatal PCP treatment produced deficits in cognition relevant to schizophrenia. Moreover, working memory function was selectively protected by the neurotrophic peptide, FGL. ..
  19. Pan Y, Wang K, Aragam N. NTM and NR3C2 polymorphisms influencing intelligence: family-based association studies. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:154-60 pubmed publisher
    ..In conclusion, our findings provide evidence that chromosome regions of 11q25 and 4q31.1 contain genes affecting IQ. This study will serve as a resource for replication in other populations. ..
  20. Muth I, Barthel K, Bahr M, Dalakas M, Schmidt J. Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of alphaB-crystallin is associated with amyloid precursor protein and accumulation of beta-amyloid. J Neurol Neurosurg Psychiatry. 2009;80:1344-9 pubmed publisher
    ..In the pathology of sporadic inclusion body myositis (sIBM), the relevance of cell stress molecules such as the heat shock protein alphaB-crystallin, particularly in healthy appearing muscle fibres, has remained elusive...
  21. Biswas S, Russell R, Jackson C, Vidovic M, Ganeshina O, Oakeshott J, et al. Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera. PLoS ONE. 2008;3:e3542 pubmed publisher
    ..Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development. ..
  22. Zhang Y, Yeh J, Richardson P, Bo X. Cell adhesion molecules of the immunoglobulin superfamily in axonal regeneration and neural repair. Restor Neurol Neurosci. 2008;26:81-96 pubmed
    ..This review will be focussed on the involvement of L1, NCAM, and polysialylated NCAM in neural repair and axon regeneration after nerve injury and their potential applications in the treatment of CNS injury. ..
  23. Mobley A, Miller A, Araneda R, Maurer L, Muller F, Greer C. Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation. J Neurosci. 2010;30:16498-508 pubmed publisher
    ..These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels. ..
  24. Campodónico P, de Kier Joffé E, Urtreger A, Lauria L, Lastiri J, Puricelli L, et al. The neural cell adhesion molecule is involved in the metastatic capacity in a murine model of lung cancer. Mol Carcinog. 2010;49:386-97 pubmed publisher
    ..NCAM may be able to modulate mechanisms involved in lung carcinoma progression and represents an attractive target to control metastatic progression. ..
  25. De Wit J, Sylwestrak E, O Sullivan M, Otto S, Tiglio K, Savas J, et al. LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation. Neuron. 2009;64:799-806 pubmed publisher
    ..These observations indicate that an LRRTM2-Neurexin1 interaction plays a critical role in regulating excitatory synapse development. ..
  26. Ko J, Fuccillo M, Malenka R, Sudhof T. LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron. 2009;64:791-8 pubmed publisher
  27. Li J, Dai G, Cheng Y, Qi X, Geng M. Polysialylation promotes neural cell adhesion molecule-mediated cell migration in a fibroblast growth factor receptor-dependent manner, but independent of adhesion capability. Glycobiology. 2011;21:1010-8 pubmed publisher
  28. Ojo B, Rezaie P, Gabbott P, Davies H, Colyer F, Cowley T, et al. Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL. Brain Behav Immun. 2012;26:778-88 pubmed publisher
    ..These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction. ..
  29. Schor I, Rascovan N, Pelisch F, Allo M, Kornblihtt A. Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc Natl Acad Sci U S A. 2009;106:4325-30 pubmed publisher
  30. Woo J, Kwon S, Kim E. The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol Cell Neurosci. 2009;42:1-10 pubmed publisher
  31. Cao J, Wang H, Yu J, Yang H, Xiao C, Gao D. Involvement of NCAM in the effects of GDNF on the neurite outgrowth in the dopamine neurons. Neurosci Res. 2008;61:390-7 pubmed publisher
    ..These results suggest that NCAM is involved in the promotive effect of GDNF on the neurite outgrowth in lesioned DA neurons, but not involved in the promotive effect of GDNF on TH expression in these neurons. ..
  32. Kataria H, Wadhwa R, Kaul S, Kaur G. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity. PLoS ONE. 2012;7:e37080 pubmed publisher
  33. Shichi K, Fujita Hamabe W, Harada S, Mizoguchi H, Yamada K, Nabeshima T, et al. Involvement of matrix metalloproteinase-mediated proteolysis of neural cell adhesion molecule in the development of cerebral ischemic neuronal damage. J Pharmacol Exp Ther. 2011;338:701-10 pubmed publisher
    ..The present findings clearly suggest that MMP-2/MMP-9-mediated NCAM proteolysis is implicated in the exacerbation of ischemic neuronal damage. ..
  34. Ojo B, Rezaie P, Gabbott P, Cowely T, Medvedev N, Lynch M, et al. A neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus. Exp Neurol. 2011;232:318-28 pubmed publisher
    ..These results demonstrate that FGL can indeed regulate neuroglial activation and reduce microglial cell density in the aged hippocampus, and support its potential use as a therapeutic agent in age-related brain disorders. ..
  35. Iijima T, Wu K, Witte H, Hanno Iijima Y, Glatter T, Richard S, et al. SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1. Cell. 2011;147:1601-14 pubmed publisher
    ..Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system...
  36. Downer E, Cowley T, Lyons A, Mills K, Berezin V, Bock E, et al. A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL. Neurobiol Aging. 2010;31:118-28 pubmed publisher
    ..These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls microglial activation. ..
  37. Bisaz R, Schachner M, Sandi C. Causal evidence for the involvement of the neural cell adhesion molecule, NCAM, in chronic stress-induced cognitive impairments. Hippocampus. 2011;21:56-71 pubmed publisher
    ..Thus, these findings support the functional involvement of NCAM in chronic stress-induced alterations and highlight this molecule as a potential target to treat stress-related cognitive disturbances. ..
  38. Aonurm Helm A, Berezin V, Bock E, Zharkovsky A. NCAM-mimetic, FGL peptide, restores disrupted fibroblast growth factor receptor (FGFR) phosphorylation and FGFR mediated signaling in neural cell adhesion molecule (NCAM)-deficient mice. Brain Res. 2010;1309:1-8 pubmed publisher
    ..We conclude that in NCAM deficient mice FGFR1-dependent signaling is disrupted and it can be restored by FGL peptide. ..
  39. Auer S, Lappalainen R, Skottman H, Suuronen R, Narkilahti S, Vikholm Lundin I. An antibody surface for selective neuronal cell attachment. J Neurosci Methods. 2010;186:72-6 pubmed publisher
    ..This study is to our knowledge the first demonstrating the use of an antibody layer as a selective surface for hESC-derived neuronal cells. ..
  40. Zhou S, Opperman K, Wang X, Chen L. unc-44 Ankyrin and stn-2 gamma-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans. Genetics. 2008;180:1429-43 pubmed publisher
    ..Furthermore, we provide molecular and genetic evidence that UNC-44 ankyrin and STN-2 gamma-syntrophin bind SAX-7 via the respective ankyrin-binding and PDZ-binding motifs to regulate SAX-7 function in maintaining neuronal positioning. ..
  41. Kochlamazashvili G, Bukalo O, Senkov O, Salmen B, Gerardy Schahn R, Engel A, et al. Restoration of synaptic plasticity and learning in young and aged NCAM-deficient mice by enhancing neurotransmission mediated by GluN2A-containing NMDA receptors. J Neurosci. 2012;32:2263-75 pubmed publisher
    ..Thus, several deficiencies of NCAM(-/-) mice can be ameliorated by enhancing GluN2A-mediated neurotransmission with DCS. ..
  42. Thompson M, Foley D, Colley K. The polysialyltransferases interact with sequences in two domains of the neural cell adhesion molecule to allow its polysialylation. J Biol Chem. 2013;288:7282-93 pubmed publisher
    ..Taken together, these results indicate that the polySTs not only recognize an acidic patch in the FN1 domain of NCAM but also must contact sequences in the Ig5 domain for polysialylation of Ig5 N-glycans to occur. ..
  43. Peixoto R, Kunz P, Kwon H, Mabb A, Sabatini B, Philpot B, et al. Transsynaptic signaling by activity-dependent cleavage of neuroligin-1. Neuron. 2012;76:396-409 pubmed publisher
    ..In turn, NLG1 cleavage depresses synaptic transmission by abruptly reducing presynaptic release probability. Thus, local proteolytic control of synaptic adhesion tunes synaptic transmission during brain development and plasticity. ..
  44. Lehembre F, Yilmaz M, Wicki A, Schomber T, Strittmatter K, Ziegler D, et al. NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin. EMBO J. 2008;27:2603-15 pubmed publisher
    ..These results establish a mechanistic link between the loss of E-cadherin expression, NCAM function, focal adhesion assembly and cell migration and invasion. ..
  45. Aonurm Helm A, Jurgenson M, Zharkovsky T, Sonn K, Berezin V, Bock E, et al. Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL. Eur J Neurosci. 2008;28:1618-28 pubmed publisher
    ..The results also suggest a role of the deficit in NCAM signalling through the FGF receptor in depression. ..
  46. Polanska U, Fernig D, Kinnunen T. Extracellular interactome of the FGF receptor-ligand system: complexities and the relative simplicity of the worm. Dev Dyn. 2009;238:277-93 pubmed publisher
    ..We will also discuss how invertebrate models such as C. elegans may advance our understanding of noncanonical FGFR signaling. ..
  47. Falconer R, Errington R, Shnyder S, Smith P, Patterson L. Polysialyltransferase: a new target in metastatic cancer. Curr Cancer Drug Targets. 2012;12:925-39 pubmed
    ..Selective inhibition of polySTs therefore presents a therapeutic opportunity to inhibit tumour invasion and metastasis. ..
  48. Saura C, Servián Morilla E, Scholl F. Presenilin/?-secretase regulates neurexin processing at synapses. PLoS ONE. 2011;6:e19430 pubmed publisher
    ..These results suggest that PS regulate the synaptic function and processing of neurexins at glutamatergic synapses, and that impaired neurexin processing by PS may play a role in FAD. ..
  49. Yoshida T, Shiroshima T, Lee S, Yasumura M, Uemura T, Chen X, et al. Interleukin-1 receptor accessory protein organizes neuronal synaptogenesis as a cell adhesion molecule. J Neurosci. 2012;32:2588-600 pubmed publisher
    ..Thus, IL-1RAcP represents an interesting molecular link between immune systems and synapse formation in the brain. ..
  50. Marino P, Norreel J, Schachner M, Rougon G, Amoureux M. A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury. Exp Neurol. 2009;219:163-74 pubmed publisher
    ..Our data point to the unique features of a carbohydrate mimicking peptide, and support the notion that PSA can be considered as an important factor in recovery from spinal cord injury. ..
  51. Francavilla C, Cattaneo P, Berezin V, Bock E, Ami D, de Marco A, et al. The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking. J Cell Biol. 2009;187:1101-16 pubmed publisher
  52. Kochlamazashvili G, Senkov O, Grebenyuk S, Robinson C, Xiao M, Stummeyer K, et al. Neural cell adhesion molecule-associated polysialic acid regulates synaptic plasticity and learning by restraining the signaling through GluN2B-containing NMDA receptors. J Neurosci. 2010;30:4171-83 pubmed publisher
  53. Rodriguez Gil D, Treloar H, Zhang X, Miller A, Two A, Iwema C, et al. Chromosomal location-dependent nonstochastic onset of odor receptor expression. J Neurosci. 2010;30:10067-75 pubmed publisher
    ..Collectively, these studies demonstrate that ORs are not equally represented in the "olfactome" across an animal's lifespan. ..