Regular Article
Analysis of Interactions of the Adhesion Molecule TAG-1 and Its Domains with Other Immunoglobulin Superfamily Members

https://doi.org/10.1006/mcne.2002.1105Get rights and content

Abstract

Cell adhesion molecules of the immunoglobulin superfamily promote cell aggregation and neurite outgrowth via homophilic and heterophilic interactions. The transient axonal glycoprotein TAG-1 induces cell aggregation through homophilic interaction of its fibronectin repeats. We investigated the domains responsible for the neurite outgrowth promoting activity of TAG-1 as well as its interactions with other cell adhesion molecules. Binding experiments with Fc-chimeric proteins revealed that TAG-1 interacts with L1, NrCAM, and F3/contactin. The membrane-associated as opposed to the soluble form of TAG-1 behaves differently in these assays. We demonstrate that both the immunoglobulin as well as the fibronectin domains promote neurite outgrowth when used as substrates. Furthermore we investigated the putative role of L1 and NrCAM as the neuronal TAG-1 receptors mediating neurite extension. DRG neurons from L1-deficient mice were found to extend neurites on TAG-1 substrates and blocking NrCAM function did not diminish the TAG-1-dependent neurite outgrowth. These results indicate that neither L1 nor NrCAM are required for TAG-1-elicited neurite outgrowth.

References (37)

  • E.T. Stoeckli et al.

    Clustering and functional co-operation of Ng-CAM and axonin-1 in the substratum-contact area of growth cones

    Dev. Biol.

    (1996)
  • P. Tsiotra et al.

    Isolation of the cDNA and chromosomal localization of the gene (TAX1) encoding the human axonal glycoprotein TAG-1

    Genomics

    (1993)
  • P. Tsiotra et al.

    The fibronectin domains of the neural adhesion molecule TAX-1 are necessary and sufficient for homophilic binding

    J. Biol. Chem.

    (1996)
  • A. Buchstaller et al.

    Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal membrane and cooperate in neurite outgrowth promotion

    J. Cell Biol.

    (1996)
  • M. Buttiglione et al.

    A functional interaction between the neuronal adhesion molecules TAG-1 and F3 modulates neurite outgrowth and fasciculation of cerebellar granule cells

    J. Neurosci.

    (1998)
  • S. Chen et al.

    Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1

    J. Neurobiol.

    (1999)
  • J.Q. Davis et al.

    Molecular composition of the node of Ranvier: Identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments

    J. Cell Biol.

    (1996)
  • E. De Angelis et al.

    Pathological missense mutations of the neural cell adhesion molecule L1 affect homophilic and heterophilic binding activities

    EMBO J.

    (1999)
  • Cited by (38)

    • Immunoglobulin cell adhesion molecules of the Ig-FNIII type and neurodevelopment

      2021, Factors Affecting Neurodevelopment: Genetics, Neurology, Behavior, and Diet
    • Distinct roles for the cell adhesion molecule Contactin2 in the development and function of neural circuits in zebrafish

      2018, Mechanisms of Development
      Citation Excerpt :

      Membrane proteins playing important roles in neurodevelopment include the cell adhesion molecules of the immunoglobulin superfamily (IgSF-CAMs), which are anchored to the membrane by a glycosylphosphatidyl inositol (GPI) linkage or a single transmembrane domain, have varying numbers of Ig-like extracellular domains, and are widely expressed during vertebrate neural development (Gennarini et al., 2017; Stoeckli, 2004; Stoeckli and Landmesser, 1995). Contactin2 (Cntn2)/Transient Axonal Glycoprotein 1 (Tag1), a GPI-linked IgSF-CAM, has six Ig-like domains and four fibronectin domains (Furley et al., 1990), and can bind homophilically (Kunz et al., 1998) as well as heterophilically with other IgSF CAMs such as L1, NgCAM, and NrCAM (Buchstaller et al., 1996; Fitzli et al., 2000; Kuhn et al., 1991; Kunz et al., 1998; Pavlou et al., 2002; Suter et al., 1995). Cntn2 can also interact with contactin-associated protein-like 2 (Caspr2) at the juxtaparanode region in neurons (Tzimourakas et al., 2007).

    • A versatile genetic tool to study midline glia function in the Drosophila CNS

      2017, Developmental Biology
      Citation Excerpt :

      More recent studies in Drosophila embryonic CNS midline have demonstrated the requirement of Nrx IV and Wrapper in neuron-glial interactions and ensheathment of commissural axons (Stork et al., 2009; Wheeler et al., 2009; Slováková and Carmena, 2011; Jacobs, 2000; Noordermeer et al., 1998). While Wrapper does not have a direct mammalian ortholog, its structure is very similar to proteins found to interact with Nrx IV/Caspr such as Cont/TAG1 (Pavlou et al., 2002). Both Wrapper and Cont are Ig-superfamily proteins with Ig/FNIII domains and are inserted in the membrane via their GPI anchors.

    • L1CAM: Cell adhesion and more

      2016, Progress in Histochemistry and Cytochemistry
      Citation Excerpt :

      The Ig-like domains are also involved in a number of heterophilic interactions. The binding partners include Ig superfamily proteins NCAM, TAG-1/axonin, F11/contactin [69,66,62]. Binding of the highly glycosylated mucin type glycoprotein CD24 depends on its modification with α2,3-sialic acid, and this interaction occurs in trans between CD24 and L1CAM at the surface of neurite outgrowth-competent cells [50].

    • Significance of F3/Contactin gene expression in cerebral cortex and nigrostriatal development

      2012, Molecular and Cellular Neuroscience
      Citation Excerpt :

      Besides that in axonal growth and pathfìnding control, axonal adhesive glycoproteins may play relevant roles in further aspects of neural development, including precursor proliferation and migration (Bizzoca et al., 2003; Lu et al., 2008; Maness and Schachner, 2007; Traka et al., 2003), synaptic contact formation and myelination (Laursen et al., 2009; Zhang et al., 2008). The involvement of such molecules in a wide set of developmental events implies that the underlying genes are tightly and coordinately regulated at the cellular levels within distinct developmental steps, which may be relevant for their functional cooperation (Bizzoca et al., 2003; Buttiglione et al., 1998; Charles et al., 2002; Hortsch et al., 2009; Pavlou et al., 2002; Pesheva et al., 2006). Among the axonally-expressed glycoproteins, F3/Contactin deserves a special mention.

    View all citing articles on Scopus
    View full text