The mouse neuronal cell surface protein F3: a phosphatidylinositol-anchored member of the immunoglobulin superfamily related to chicken contactin.

Abstract

Abstract. Several members of the Ig superfamily are expressed on neural cells where they participate in surface interactions between cell bodies and processes. Their Ig domains are more closely related to each other than to Ig variable and constant domains and have been grouped into the C2 set. Here, we report the cloning and characterization of another member of this group, the mouse neuronal cell surface antigen F3. The F3 eDNA sequence contains an open reading frame that could encode a 1,020-amino acid protein consisting of a signal sequence, six Ig-like domains of the C2 type, a long premembrane region containing two segments that exhibit sequence similarity to fibronectin type III repeats and a moderately hydrophobic COOH-terminal sequence. The protein does not contain a typical transmembrane segment but appears to be attached to the membrane by a phosphatidylinositol anchor. Antibodies against the F3 protein recognize a prominent 135-kD protein in mouse brain. In fetal brain cultures, they stain the neuronal cell surface and, in cultures maintained in chemically defined medium, most prominently neurites and neurite bundles. The mouse f3 gene maps to band F of chromosome 15. The gene transcripts detected in the brain by F3 cDNA probes are developmentally regulated, the highest amounts being expressed between 1 and 2 wk after birth.The F3 nucleotide and deduced amino acid sequence show striking similarity to the recently published sequence of the chicken neuronal cell surface protein contactin. However, there are important differences between the two molecules. In contrast to F3, contactin has a transmembrane and a cytoplasmic domain. Whereas contactin is insoluble in nonionic detergent and is tightly associated with the cytoskeleton, about equal amounts of F3 distribute between buffer-soluble, nonionic detergent-soluble, and detergent-insoluble fractions. Among other neural cell surface proteins, F3 most resembles the neuronal cell adhesion protein L1, with 25 % amino acid identity between their extracellular domains. Based on its structural similarity with known cell adhesion proteins of nervous tissue and with L1 in particular, we propose that F3 mediates cell surface interactions during nervous system development.

The axonally secreted cell adhesion molecule, axonin‐1

“…Chicken F11 and contactin, which are very close relatives or identical (Bruemmendorf et al, 1989), and F3, which is their presumed homologue in the mouse (Gennarini et al, 1989), have an amino acid sequence identity with both axonin-I and TAG-I of approximately 50%. The overall domain structure of axonin-I is identical to that of TAG-I, Ff 1, and F3, including six Ig and four FNIII domains.…”

“…The deduced amino acid sequence of axonin-1 was compared with the NBRF-PIR protein database (release 25,1990), and especially to all the sequences of neural cell adhesion molecules of the Ig/FNIII subfamily available to date, including rat TAG-1 (Furley et al, 1990), chicken F11 (Bruemmendorf et al, 1989) and contactin (Ranscht, 1988), mouse F3 (Gennarini et al, 1989), chicken Ng-CAM (Burgoon et al, 1991), chicken Nr-CAM (Grumet et al, 1991), mouse L1 (Moos et al, 1988), and chicken N-CAM (Cunningham et al, 1987). The highest degree of similarity was found to the sequence of rat TAG-I.…”

“…The members of the other subgroup of AxCAMs with Ig/FNIIi subfamily traits are composed of six Ig and four FNIII domains, viz. contactin/Fll of the chicken (Ranscht, 1988;Bruemmendorf et al, 1989), F3, the putative mouse homologue of contactin/Fll (Gennarini et al, 1989) and TAG-I of the rat (Furley et al, 1990). The molecular characterization of the axonin-I cDNA reported in this study suggests that axonin-I is another member of the second group.…”

Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface

“…Contactin, a glycosyl-phosphatidylinositol (GPI)-anchored protein that is expressed in neurons and glia (Ranscht, 1988;Brummendorf et al, 1989;Gennarini et al, 1989), associates with Na v 1.2 in vivo via the ␤1-subunit and enhances the channel density at the plasma membrane (Kazarinova-Noyes et al, 2001). The interaction of contactin and Na v 1.9, which is mediated by the C terminus of the channel (C. , probably requires a cellular linker, for example a ␤-subunit.…”

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

“…Contactin is expressed by a diversity of neurons and contributes to the formation and function of neuronal connections (8)(9)(10). In myelinated peripheral nerves, Contactin is concentrated at axon membranes flanking the nodes of Ranvier, and serves an essential role in organizing the septate-like paranodal axoglial junctions (11,12).…”