neuronal cell adhesion molecules


Summary: Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.

Top Publications

  1. Yip Y, Mehta N, Magdaleno S, Curran T, Yip J. Ectopic expression of reelin alters migration of sympathetic preganglionic neurons in the spinal cord. J Comp Neurol. 2009;515:260-8 pubmed publisher
    ..These results show that SPN position can change with location and level of reelin expression. Possible functions of Reelin on SPN migration are discussed. ..
  2. Gaiano N. Strange bedfellows: Reelin and Notch signaling interact to regulate cell migration in the developing neocortex. Neuron. 2008;60:189-91 pubmed publisher
    ..In this issue of Neuron, Rakic and colleagues report that Notch signaling, long known to regulate neural stem cells, also plays a critical role in mediating the effects of Reelin on neuronal cell migration. ..
  3. Rosso O, Piazza T, Bongarzone I, Rossello A, Mezzanzanica D, Canevari S, et al. The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells. Mol Cancer Res. 2007;5:1246-53 pubmed publisher
    ..Altogether, our data suggest that the disruption of ALCAM-mediated adhesion is a relevant step in EOC motility, and ADAM17/TACE takes part in this process, which may be relevant to EOC invasive potential. ..
  4. Larson D, Liberman Z, Cagan R. Cellular behavior in the developing Drosophila pupal retina. Mech Dev. 2008;125:223-32 pubmed publisher
    ..Based upon our live visualization of the P120-Catenin mutant as well as genetic data, we conclude that P120-Catenin is acting to stabilize E-cadherin and adherens junction integrity during eye development. ..
  5. Levenson J, Qiu S, Weeber E. The role of reelin in adult synaptic function and the genetic and epigenetic regulation of the reelin gene. Biochim Biophys Acta. 2008;1779:422-31 pubmed publisher
  6. Cooper J. A mechanism for inside-out lamination in the neocortex. Trends Neurosci. 2008;31:113-9 pubmed publisher
    ..This 'detach and go' model explains many aspects of inside-out lamination, defects in the Reeler mutant and results of recent genetic and in utero experiments. ..
  7. Li J, Ashley J, Budnik V, Bhat M. Crucial role of Drosophila neurexin in proper active zone apposition to postsynaptic densities, synaptic growth, and synaptic transmission. Neuron. 2007;55:741-55 pubmed
    ..Together, our results provide compelling evidence for an in vivo role of neurexins in the modulation of synaptic architecture and adhesive interactions between pre- and postsynaptic compartments. ..
  8. Johnson R, Seppa M, Cagan R. The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning. J Cell Biol. 2008;180:1191-204 pubmed publisher
    ..Together, these data demonstrate that Cindr is involved in dynamic cell rearrangement in an emerging epithelium. ..
  9. Wang K, Zhang H, Ma D, Bucan M, Glessner J, Abrahams B, et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459:528-33 pubmed publisher
    ..Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs. ..

More Information


  1. Biswas S, Reinhard J, Oakeshott J, Russell R, Srinivasan M, Claudianos C. Sensory regulation of neuroligins and neurexin I in the honeybee brain. PLoS ONE. 2010;5:e9133 pubmed publisher
  2. Katsuyama Y, Terashima T. Developmental anatomy of reeler mutant mouse. Dev Growth Differ. 2009;51:271-86 pubmed publisher
    ..Based on this overview of the reeler abnormalities, we discuss possible function of Reelin signal in the neuronal migration and other morphological events in mouse development...
  3. Weichenhan D, Traut W, Göngrich C, Himmelbauer H, Busch L, Monyer H, et al. A mouse translocation associated with Caspr5-2 disruption and perinatal lethality. Mamm Genome. 2008;19:675-86 pubmed publisher
    ..We, therefore, suspect that Caspr5-2 disruption leads to dysfunction at the cellular level rather than at the level of organ development. ..
  4. Mezzanzanica D, Fabbi M, Bagnoli M, Staurengo S, Losa M, Balladore E, et al. Subcellular localization of activated leukocyte cell adhesion molecule is a molecular predictor of survival in ovarian carcinoma patients. Clin Cancer Res. 2008;14:1726-33 pubmed publisher
    ..5). Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer patients and might help to identify patients who could benefit from more frequent follow-up or alternative therapeutic modalities. ..
  5. Barrow S, Constable J, Clark E, El Sabeawy F, McAllister A, Washbourne P. Neuroligin1: a cell adhesion molecule that recruits PSD-95 and NMDA receptors by distinct mechanisms during synaptogenesis. Neural Dev. 2009;4:17 pubmed publisher
    ..Our results suggest that axodendritic contact leads to rapid accumulation of Nlg1, recruitment of NMDARs co-transported with Nlg1 soon thereafter, followed by a slower, independent recruitment of PSD-95 to those nascent synapses. ..
  6. Horst D, Kriegl L, Engel J, Kirchner T, Jung A. Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest. 2009;27:844-50 pubmed publisher
    ..We show that CD133 is the best sole marker to predict low patient survival, while the combined analysis of all three markers may be superior in identification of low-, intermediate-, and high-risk cases of colorectal cancer. ..
  7. Zweier C, de Jong E, Zweier M, Orrico A, Ousager L, Collins A, et al. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet. 2009;85:655-66 pubmed publisher
    ..We therefore propose that an analogous shared synaptic mechanism contributes to the similar clinical phenotypes resulting from defects in human NRXN1 and CNTNAP2. ..
  8. Feng L, Allen N, Simo S, Cooper J. Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development. Genes Dev. 2007;21:2717-30 pubmed
    ..The results implicate Cul5 and SOCS proteins in down-regulation of Dab1 in vivo and show that Cul5 plays an essential role in regulating neuron migrations during cortical development, possibly by opposing a promigratory effect of Dab1. ..
  9. Catania E, Pimenta A, Levitt P. Genetic deletion of Lsamp causes exaggerated behavioral activation in novel environments. Behav Brain Res. 2008;188:380-90 pubmed publisher
    ..Genetic deletion of Lsamp may thus cause circumscribed changes in the fine connectivity of specific circuits that underlie these behaviors. ..
  10. Katidou M, Vidaki M, Strigini M, Karagogeos D. The immunoglobulin superfamily of neuronal cell adhesion molecules: lessons from animal models and correlation with human disease. Biotechnol J. 2008;3:1564-80 pubmed publisher
    b>Neuronal cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) play a crucial role in the formation of neural circuits at different levels: cell migration, axonal and dendritic targeting as well as synapse formation...
  11. Patel B, Yu Y, Du J, Levi E, Phillip P, Majumdar A. Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: a risk factor for colon cancer. Biochem Biophys Res Commun. 2009;378:344-7 pubmed publisher
    ..Moreover, our observation of the age-related rise in CSC in macroscopically normal colonic mucosa suggests a predisposition of the organ to developing colorectal cancer. ..
  12. Roodink I, Kats G, van Kempen L, Grunberg M, Maass C, Verrijp K, et al. Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression. Am J Pathol. 2008;173:1873-81 pubmed publisher
    ..These results show that PLXND1 expression during tumor development is strongly correlated with both invasive behavior and metastasis, but exclude Sema3E as an activating ligand. ..
  13. Hashimoto Torii K, Torii M, Sarkisian M, Bartley C, Shen J, Radtke F, et al. Interaction between Reelin and Notch signaling regulates neuronal migration in the cerebral cortex. Neuron. 2008;60:273-84 pubmed publisher
    ..Finally, our in vitro biochemical studies show that Reelin signaling inhibits Notch ICD degradation via Dab1. Together, our results indicate that neuronal migration in the developing cerebral cortex requires a Reelin-Notch interaction. ..
  14. Groc L, Choquet D, Stephenson F, Verrier D, Manzoni O, Chavis P. NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein Reelin. J Neurosci. 2007;27:10165-75 pubmed
    ..Our data reveal a new mode of control of synaptic NMDAR assembly at postnatal hippocampal synapses and an unprecedented role of ECM proteins in regulating glutamate receptor surface diffusion. ..
  15. Cabrera Socorro A, Hernandez Acosta N, Gonzalez Gomez M, Meyer G. Comparative aspects of p73 and Reelin expression in Cajal-Retzius cells and the cortical hem in lizard, mouse and human. Brain Res. 2007;1132:59-70 pubmed
  16. Jossin Y, Gui L, Goffinet A. Processing of Reelin by embryonic neurons is important for function in tissue but not in dissociated cultured neurons. J Neurosci. 2007;27:4243-52 pubmed
  17. Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, et al. Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO J. 2007;26:1373-84 pubmed
    ..The effects of Sema4A on endothelial cells are dependent on its ability to suppress VEGF-mediated Rac activation and integrin-dependent cell adhesion. It thus appears that Sema4A-Plexin-D1 signaling negatively regulates angiogenesis. ..
  18. Maurel P, Einheber S, Galinska J, Thaker P, Lam I, Rubin M, et al. Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination. J Cell Biol. 2007;178:861-74 pubmed
    ..These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo-glial interactions along the internode. ..
  19. Santos J, Vömel M, Struck R, Homberg U, Nässel D, Wegener C. Neuroarchitecture of peptidergic systems in the larval ventral ganglion of Drosophila melanogaster. PLoS ONE. 2007;2:e695 pubmed
    ..The data can further be useful to identify colocalized transmitters and receptors, and develop peptidergic neurons as new landmarks. ..
  20. Maertens B, Hopkins D, Franzke C, Keene D, Bruckner Tuderman L, Greenspan D, et al. Cleavage and oligomerization of gliomedin, a transmembrane collagen required for node of ranvier formation. J Biol Chem. 2007;282:10647-59 pubmed
    ..Interestingly, the later cleavage induces formation of higher order, insoluble molecular aggregates that may play important roles in Na(+)-channel clustering. ..
  21. Wu V, Yu M, Paik R, Banerjee S, Liang Z, Paul S, et al. Drosophila Varicose, a member of a new subgroup of basolateral MAGUKs, is required for septate junctions and tracheal morphogenesis. Development. 2007;134:999-1009 pubmed
    ..Thus, Vari fundamentally extends the similarity of Drosophila and vertebrate basolateral regions from sharing only polarity complexes to sharing both polarity and cell-adhesion complexes. ..
  22. Ina A, Sugiyama M, Konno J, Yoshida S, Ohmomo H, Nogami H, et al. Cajal-Retzius cells and subplate neurons differentially express vesicular glutamate transporters 1 and 2 during development of mouse cortex. Eur J Neurosci. 2007;26:615-23 pubmed
  23. Zeng X, Sun M, Liu L, Chen F, Wei L, Xie W. Neurexin-1 is required for synapse formation and larvae associative learning in Drosophila. FEBS Lett. 2007;581:2509-16 pubmed
    ..The synapse number is decreased in central nervous system in Neurexin-1 null mutants. In addition, Neurexin-1 null mutants exhibit associative learning defect in larvae. ..
  24. Eshed Y, Feinberg K, Carey D, Peles E. Secreted gliomedin is a perinodal matrix component of peripheral nerves. J Cell Biol. 2007;177:551-62 pubmed
    ..Our results indicate that the deposition of gliomedin multimers at the nodal gap by binding to HSPGs facilitates the clustering of the axonodal CAMs and Na(+) channels. ..
  25. Dong E, Guidotti A, Grayson D, Costa E. Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters. Proc Natl Acad Sci U S A. 2007;104:4676-81 pubmed
  26. Chin J, Massaro C, Palop J, Thwin M, Yu G, Bien Ly N, et al. Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease. J Neurosci. 2007;27:2727-33 pubmed
    ..We conclude that alterations in Reelin processing or signaling may be involved in AD-related neuronal dysfunction. ..
  27. Zhuang S, Kelo L, Nardi J, Kanost M. Neuroglian on hemocyte surfaces is involved in homophilic and heterophilic interactions of the innate immune system of Manduca sexta. Dev Comp Immunol. 2007;31:1159-67 pubmed
    ..The Ig domains of neuroglian are involved in both homophilic and heterophilic interactions, and subsets of these six different Ig domains may affect different functions of neuroglian. ..
  28. Spiegel I, Adamsky K, Eshed Y, Milo R, Sabanay H, Sarig Nadir O, et al. A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination. Nat Neurosci. 2007;10:861-9 pubmed
    ..These results suggest that Necl proteins are important for mediating axon-glia contact during myelination in peripheral nerves. ..
  29. Qiu S, Weeber E. Reelin signaling facilitates maturation of CA1 glutamatergic synapses. J Neurophysiol. 2007;97:2312-21 pubmed
  30. Qiu S, Zhao L, Korwek K, Weeber E. Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. J Neurosci. 2006;26:12943-55 pubmed
    ..Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus. ..
  31. Zhuang S, Shao H, Guo F, Trimble R, Pearce E, Abmayr S. Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes. Development. 2009;136:2335-44 pubmed publisher
    ..These data reveal significant similarities between the insect ND and the SD in mammalian podocytes at the level of structure and function. ..
  32. Wilke S, Krausze J, Gossen M, Groebe L, Jäger V, Gherardi E, et al. Glycoprotein production for structure analysis with stable, glycosylation mutant CHO cell lines established by fluorescence-activated cell sorting. Protein Sci. 2010;19:1264-71 pubmed publisher
    ..The combination of FACS and gene excision described here constitutes a robust and fast procedure for maximizing the yield of glycoproteins for structural analysis from glycosylation mutant cell lines. ..
  33. Cardoso C, Martínez A, Guimaraes P, Mendes C, Pacheco A, de Oliveira R, et al. Ninjurin 1 asp110ala single nucleotide polymorphism is associated with protection in leprosy nerve damage. J Neuroimmunol. 2007;190:131-8 pubmed
    ..Nevertheless, ala110 was associated with functional nerve impairment (OR=2.42; p=0.02 for ala/ala) and with lower mRNA levels. Our data suggests that asp110ala could be a valuable genetic marker of nerve damage in leprosy. ..
  34. Gregorio S, Sallet P, Do K, Lin E, Gattaz W, Dias Neto E. Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence. Psychiatry Res. 2009;165:1-9 pubmed publisher
    ..Although our results are preliminary, due to the small number of individuals analyzed, such an approach could reveal new candidate genes implicated in anomalous neurodevelopment in schizophrenia. ..
  35. Fogel A, Akins M, Krupp A, Stagi M, Stein V, Biederer T. SynCAMs organize synapses through heterophilic adhesion. J Neurosci. 2007;27:12516-30 pubmed
    ..Our results define SynCAM proteins as components of novel heterophilic transsynaptic adhesion complexes that set up asymmetric interactions, with SynCAM proteins contributing to synapse organization and function. ..
  36. Tsai N, Tsui Y, Pintar J, Loh H, Wei L. Kappa opioid receptor contributes to EGF-stimulated neurite extension in development. Proc Natl Acad Sci U S A. 2010;107:3216-21 pubmed publisher
    ..The result also reveals an action of EGF to augment posttranscriptional regulation of certain mRNAs during developmental stages. ..
  37. Caprile T, Osorio G, Henriquez J, Montecinos H. Polarized expression of integrin beta1 in diencephalic roof plate during chick development, a possible receptor for SCO-spondin. Dev Dyn. 2009;238:2494-504 pubmed publisher
    ..Our results suggest that SCO-spondin has a role in the development of the PC through its interaction with integrin beta1. ..
  38. Boutin C, Schmitz B, Cremer H, Diestel S. NCAM expression induces neurogenesis in vivo. Eur J Neurosci. 2009;30:1209-18 pubmed publisher
    ..These results suggest that heterophilic interactions of NCAM with other components of the cell membrane must be involved. ..
  39. Fuentealba P, Klausberger T, Karayannis T, Suen W, Huck J, Tomioka R, et al. Expression of COUP-TFII nuclear receptor in restricted GABAergic neuronal populations in the adult rat hippocampus. J Neurosci. 2010;30:1595-609 pubmed publisher
    ..The characterization of COUP-TFII-expressing neurons suggests that this developmentally important transcription factor plays cell type-specific role(s) in the adult hippocampus. ..
  40. Niederkofler V, Baeriswyl T, Ott R, Stoeckli E. Nectin-like molecules/SynCAMs are required for post-crossing commissural axon guidance. Development. 2010;137:427-35 pubmed publisher
    ..It is expressed by floorplate cells and interacts with Necls/SynCAMs expressed by commissural axons to mediate a turning response in post-crossing commissural axons. ..
  41. Chen S, Tari P, She K, Haas K. Neurexin-neuroligin cell adhesion complexes contribute to synaptotropic dendritogenesis via growth stabilization mechanisms in vivo. Neuron. 2010;67:967-83 pubmed publisher
  42. Vavlitou N, Sargiannidou I, Markoullis K, Kyriacou K, Scherer S, Kleopa K. Axonal pathology precedes demyelination in a mouse model of X-linked demyelinating/type I Charcot-Marie Tooth neuropathy. J Neuropathol Exp Neurol. 2010;69:945-58 pubmed publisher
    ..These findings demonstrate that axonal abnormalities including impaired cytoskeletal organization and defects in axonal transport precede demyelination in this mouse model of CMT1X. ..
  43. Hishimoto A, Liu Q, Drgon T, Pletnikova O, Walther D, Zhu X, et al. Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Hum Mol Genet. 2007;16:2880-91 pubmed
  44. Aisa B, Elizalde N, Tordera R, Lasheras B, Del Rio J, Ramirez M. Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: implications for spatial memory. Hippocampus. 2009;19:1222-31 pubmed publisher
    ..Altogether these results suggest that MS can alter normal brain development, providing a potential mechanism by which early environmental stressors may influence vulnerability to show cognitive impairments later in life. ..
  45. Simon G, Hu Y, Khan A, Zhou J, Salmon J, Chikhlikar P, et al. Dendritic cell mediated delivery of plasmid DNA encoding LAMP/HIV-1 Gag fusion immunogen enhances T cell epitope responses in HLA DR4 transgenic mice. PLoS ONE. 2010;5:e8574 pubmed publisher
  46. Doehner J, Madhusudan A, Konietzko U, Fritschy J, Knuesel I. Co-localization of Reelin and proteolytic AbetaPP fragments in hippocampal plaques in aged wild-type mice. J Alzheimers Dis. 2010;19:1339-57 pubmed publisher
    ..Our results suggest that Reelin itself aggregates into abnormal oligomeric or protofibrillary deposits during aging, potentially creating a precursor condition for fibrillary amyloid-beta plaque formation. ..
  47. Lee H, Ahn B, Shin M, Choi J, Kim K. Ninjurin1: a potential adhesion molecule and its role in inflammation and tissue remodeling. Mol Cells. 2010;29:223-7 pubmed publisher
  48. Fu Z, Vicini S. Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells. Mol Cell Neurosci. 2009;42:45-55 pubmed publisher
    ..Taken all together, we propose that NLG-2 plays important functional role in inhibitory synapse development and maturation. ..
  49. Harris E, Weigel P. The ligand-binding profile of HARE: hyaluronan and chondroitin sulfates A, C, and D bind to overlapping sites distinct from the sites for heparin, acetylated low-density lipoprotein, dermatan sulfate, and CS-E. Glycobiology. 2008;18:638-48 pubmed publisher
    ..These results enable us to outline, for the first time, a binding activity map for multiple ligands of HARE. ..
  50. Suckow A, Comoletti D, Waldrop M, Mosedale M, Egodage S, Taylor P, et al. Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology. 2008;149:6006-17 pubmed publisher
    ..Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus...
  51. Kolozsi E, MacKenzie R, Roullet F, deCatanzaro D, Foster J. Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice. Neuroscience. 2009;163:1201-10 pubmed publisher
    ..This lowered expression may be linked to autistic-like behavioral phenotype observed in the VPA mice. ..
  52. Forster E, Bock H, Herz J, Chai X, Frotscher M, Zhao S. Emerging topics in Reelin function. Eur J Neurosci. 2010;31:1511-8 pubmed publisher
    ..The present review has been inspired by a session entitled 'Functions of Reelin in the developing and adult hippocampus', held at the Spring Hippocampal Research Conference in Verona/Italy, June 2009. ..
  53. Park S, Jung M, Kim I. Stabilin-2 mediates homophilic cell-cell interactions via its FAS1 domains. FEBS Lett. 2009;583:1375-80 pubmed publisher
    ..Together, these data show the participation of stabilin-2 in homophilic cell adhesion and role of FAS1 domains. ..