Isolation of the cDNA and Chromosomal Localization of the Gene (TAX1) Encoding the Human Axonal Glycoprotein TAG-1

doi:10.1016/S0888-7543(05)80357-X

Genomics

Volume 18, Issue 3, December 1993, Pages 562-567

https://doi.org/10.1016/S0888-7543(05)80357-X Get rights and content

Abstract

The transient axonal glycoprotein (TAG-1) is a cell adhesion molecule that promotes neurite outgrowth and belongs to the immunoglobulin superfamily. We have isolated cDNAs encoding TAX1, the human homologue of TAG-1. Human TAX1 shows a high degree of homology to rat TAX1 and less to its chick counterpart, axonin-1, with 91 and 75% identity at the amino acid level, respectively. The numbers of immunoglobulin (IgC2) domains and fibronectin repeats present in TAG-1 are conserved among the three species. The highest degree of conservation occurs in the second IgC2 domain (98% with the rat and 82% with the chick). The human homologue also contains a putative N-terminal signal sequence and a C-terminal hydrophobic sequence, suggestive of linkage to the cell membrane via phosphatidylinositol. In addition, the two mammalian TAG-1 proteins share the RGD tripeptide, a motif known to mediate recognition of fibronectin by integrins. In situ hybridization to human metaphase chromosomes maps the TAX1 gene encoding human TAG-1 to a single location on chromosome 1q32.

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Cited by (26)

The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders
2017, Molecular and Cellular Neuroscience
Citation Excerpt :
Since much of the work on the early roles of contactins, and on their roles in dictating the distribution of ion channels in myelinated axons, relates to Contactins 1 and Contactin 2, this review article focuses on these proteins, while the functional roles of Contactins 3 to 6 have recently been explored (Mohebiany et al., 2014; Zuko et al., 2011), and will be part of a different review article from Burbach and coworkers in this same Special Issue. Contactin 1 is the name given to an axonal adhesive glycoprotein originally denominated Contactin or F11 in chick (Ranscht, 1988; Brümmendorf et al., 1989) and F3 in rodents (Gennarini et al., 1989 a,b), while Contactin 2 was formerly denominated Transient Axonal Glycoprotein (TAG-1) in rodents (Yamamoto et al., 1986; Dodd et al., 1988; Furley et al., 1990), Axonin1 in chick (Ruegg et al., 1989; Zuellig et al., 1992) and TAX-1 in humans (Tsiotra et al., 1993; Hasler et al., 1993). Contactins 1 and 2 are closely related to each other in structural terms, sharing a nearly 50% identity at the aminoacid level (Fig. 1) and a similar overall organisation (Fig. 2A).
This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1–6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~ 50 (49.38)% identity at the aminoacid level. They are components of the cell surface, from which they may be released in soluble forms. They bind heterophilically to multiple partners in cis and in trans, including members of the related L1CAM family and of the Neurexin family Contactin-associated proteins (CNTNAPs or Casprs). Such interactions are important for organising the neuronal membrane, as well as for modulating the growth and pathfinding of axon tracts. In addition, they also mediate the functional maturation of axons by promoting their interactions with myelinating cells at the nodal, paranodal and juxtaparanodal regions. Such interactions also mediate differential ionic channels (both Na⁺ and K⁺) distribution, which is of critical relevance in the generation of the peak-shaped action potential. Indeed, thanks to their interactions with Ankyrin G, Na⁺ channels map within the nodal regions, where they drive axonal depolarization. However, no ionic channels are found in the flanking Contactin1-containing paranodal regions, where CNTN1 interactions with Caspr1 and with the Ig superfamily component Neurofascin 155 in cis and in trans, respectively, build a molecular barrier between the node and the juxtaparanode. In this region K⁺ channels are clustered, depending upon molecular interactions with Contactin 2 and with Caspr2.
In addition to these functions, the Contactins appear to have also a role in degenerative and inflammatory disorders: indeed Contactin 2 is involved in neurodegenerative disorders with a special reference to the Alzheimer disease, given its ability to work as a ligand of the Alzheimer Precursor Protein (APP), which results in increased Alzheimer Intracellular Domain (AICD) release in a γ-secretase-dependent manner. On the other hand Contactin 1 drives Notch signalling activation via the Hes pathway, which could be consistent with its ability to modulate neuroinflammation events, and with the possibility that Contactin 1-dependent interactions may participate to the pathogenesis of the Multiple Sclerosis and of other inflammatory disorders.
Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes
2008, Molecular and Cellular Neuroscience
The cell adhesion molecule TAG-1 is expressed by neurons and glial cells and plays a role in axon outgrowth, migration and fasciculation during development. TAG-1 is also required for the clustering of Kv1.1/1.2 potassium channels and Caspr2 at the juxtaparanodes of myelinated fibers. Behavioral examination of TAG-1 deficient mice (Tag-1^−/−) showed cognitive impairments in the Morris water maze and novel object recognition tests, reduced spontaneous motor activity, abnormal gait coordination and increased response latency to noxious stimulation. Investigation at the molecular level revealed impaired juxtaparanodal clustering of Caspr2 and Kv1.1/1.2 in the hippocampus, entorhinal cortex, cerebellum and olfactory bulb, with diffusion into the internode. Caspr2 and Kv1.1 levels were reduced in the cerebellum and olfactory bulb. Moreover, Tag-1^−/− mice had shorter internodes in the cerebral and cerebellar white matter. The detected molecular alterations may account for the behavioural deficits and hyperexcitability in these animals.
The upstream regulatory region of the gene for the human homologue of the adhesion molecule TAG-1 contains elements driving neural specific expression in vivo
2003, Molecular Brain Research
Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) exhibit restricted spatial and temporal expression profiles requiring a tight regulatory program during development. The rodent glycoprotein TAG-1 and its orthologs TAX-1 in the human and axonin-1 in chick are cell adhesion molecules belonging to the contactin/F3 subgroup of the IgSF. TAG-1 is expressed in restricted subsets of central and peripheral neurons, not only during development but also in adulthood, and is implicated in neurite outgrowth, axon guidance and fasciculation, as well as neuronal migration. In an attempt to identify the regulatory elements that guide the neuronal expression of TAG-1, we have isolated genomic clones containing 4 kb of the TAX-1 upstream sequence and used them to drive the expression of the LacZ reporter gene in transgenic mice. We demonstrate that this sequence includes elements not only sufficient to restrict expression to the nervous system, but also to recapitulate to a great extent the endogenous pattern of the TAG-1 expression in the developing CNS.
F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation
2003, Cell
Axon-derived molecules are temporally and spatially required as positive or negative signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation. The GPI-linked neural cell recognition molecule F3/contactin is clustered during development at the paranodal region, a vital site for axoglial interaction. Here, we show that F3/contactin acts as a functional ligand of Notch. This trans-extracellular interaction triggers γ-secretase-dependent nuclear translocation of the Notch intracellular domain. F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination.
Analysis of interactions of the adhesion molecule TAG-1 and its domains with other immunoglobulin superfamily members
2002, Molecular and Cellular Neuroscience
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.
Expression and regulation of a gene encoding neural recognition molecule NB-3 of the contactin/F3 subgroup in mouse brain
2000, Gene
NB-3 is a neural recognition molecule which is a member of contactin/F3 subgroup in the immunoglobulin superfamily. We report here the developmental expression pattern and localization of NB-3 mRNA in mouse brain, determination of the NB-3 gene organization and identification of the promoter region. We also describe a splicing isoform of mouse NB-3. Mouse NB-3 exhibited 96% identity with rat NB-3 at the amino acid sequence level. The splicing isoform lacked the amino acid residues between 62 and 78 of the original NB-3, which constituted a part of the first immunoglobulin-like domain. The expression of NB-3 mRNA was evident after birth, reaching a maximum at the postnatal seventh day, and declined thereafter in the cerebrum, whereas the mRNA increased in the cerebellum to adulthood. In situ hybridization demonstrated that NB-3 mRNA was preferentially expressed in the accessory olfactory bulb, layers II/III and V of the cerebral cortex, piriform cortex, anterior thalamic nuclei, locus coeruleus of the pons and mesencephalic trigeminal nucleus, and in Purkinje cells of the cerebellum. The mouse NB-3 gene consisted of 23 exons spanning more than 130 kb. The overall organization of the gene was similar to those of the F11, axonin-1 and TAX-1 genes of the subgroup. By reporter gene analysis with the 5′-flanking region of the gene, we found a basal promoter activity in the 1.2 kb fragment upstream of the putative transcription initiation site. This study provides a basis for elucidating the biological significance of the contactin/F3 subgroup molecules.

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¹: The nucleotide sequence data reported in this paper have been submittedto the GenBank/EMBL Data Libraries under Accession No. X67734.

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Isolation of the cDNA and Chromosomal Localization of the Gene (TAX1) Encoding the Human Axonal Glycoprotein TAG-11

Abstract

Neuron

Cell

Neuron

Cell

Neuron

Genomics

Cell

Neuron

Cell

Neuron

Semin. Neurosci.

Genomics

Lip pits and deletion 1q32-q41

Am. J. Med. Genet.

Genomic sequencing

Axon guidance and the patterning of neural projections in vertebrates

Science

Identification of a chromosome 18q gene that is altered in colorectal cancers

Science

Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures

Anna. Rev. Biochem.