Structural Features of a Close Homologue of L1 (CHL1)in the Mouse: A New Member of the L1 Family of Neural Recognition Molecules

Abstract

We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N-terminal signal sequence, six immunoglobulin (Ig)-like domains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane domain and a C-terminal, most likely intracellular domain of approximately 100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng-CAM (approximately 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zebrafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (approximately 27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most similar to mouse and chicken Nr-CAM, mouse and rat neurofascin (approximately 60% amino acid identity) followed by chicken neurofascin and Ng-CAM, Drosophila neuroglian and zebrafish L1.1 and L1.2 (approximately 40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosophila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/rat ankyrin-binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig-like domains and FN-like repeats. These show a collinearity in the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI-linked forms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mouse PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cancer molecule (DCC), previously introduced as an N-CAM-like molecule, conforms to the L1 family cassette. Other structural features of CHL 1 shared between members of the L1 family are a high degree of N-glycosidically linked carbohydrates (approximately 20% of its molecular mass), which include the HNK-1 carbohydrate structure, and a pattern of protein fragments comprising a major 185 kDa band and smaller fragments of 165 and 125 kDa. As for the other L1 family members, predominant expression of CHL1 is observed in the nervous system and at later developmental stages. In the central nervous system CHL1 is expressed by neurons, but, in contrast to L1, also by glial cells. Our findings suggest a common ancestral L1-like molecule which evolved via gene duplication to generate a diversity of structurally and functionally distinct yet similar molecules.

Expression of an L1-Related Cell Adhesion Molecule on Developing CNS Fiber Tracts in Zebrafish and Its Functional Contribution to Axon Fasciculation

“…Thus, it seems likely that there exist three L1-like molecules in zebrafish (Hortsch, 1996). Moreover, a close relative of L1, CH-L1, was recently discovered in mouse (Holm et al, 1996), and NrCAM represents an additional member of L1-related CAMs in chick .…”

“…E587 Ag belongs to the L1 subfamily of the immunoglobulin superfamily of cell adhesion molecules (Ig CAM) which includes mammalian L1 (Rathjen and Schachner, 1984), mouse CHL1 (Holm et al, 1996), chick G4/Ng-CAM Burgoon et al, 1991), and zebrafish L1.1 and L1.2 (Tongiorgi et al, 1995). From the comparison of the predicted amino acid sequences it seems unlikely that E587 Ag is the direct homolog of one of the above molecules but may therefore represent an additional member of the L1 subfamily (Giordano et al, 1997;Hortsch, 1996).…”

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

“…Among the recognition molecules of the Ig superfamily, the close homolog of L1 (CHL1) was discovered as a novel member of the L1 family (Holm et al, 1996;Hillenbrand et al, 1999). Like L1, CHL1 promotes neurite outgrowth and neuronal survival, when substratecoated in vitro (Chen et al, 1999) and, as a coreceptor with integrins, enhances cell migration (Holm et al, 1996;Hillenbrand et al, 1999;Buhusi et al, 2003).…”

An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia

“…A recently identified close homologue of L1 (CHL1, also called CALL (cell adhesion L1-like)) is a member of this family and is a powerful promoter of neurite outgrowth. 14,15 CHL1 is expressed during brain development at times of neurite outgrowth. Expression of CHL1 and L1CAM show overlapping but distinct patterns in neurons and glia, suggesting differential effects of L1-like molecules on neurite outgrowth.…”