STRUCTURAL FEATURES OF A CLOSE HOMOLOG OF L1 (CHL1) IN THE MOUSE - A NEW MEMBER OF THE L1 FAMILY OF NEURAL RECOGNITION MOLECULES

We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 c omprises an N-terminal Signal sequence, six immunoglobulin (Ig)-like d omains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane do main and a C-terminal, most likely intracellular domain of similar to 100 amino acids. CHL1 is most similar in its extracellular domain to c hicken Ng-CAM (similar to 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zeb rafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (similar to 27% amino acid identity). The similarity with ot her members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most s imilar to mouse and chicken Nr-CAM, mouse and rat neurofascin (similar to 60% amino acid identity) followed by chicken neurofascin and Ng-CA M, Drosophila neuroglian and zebrafish L1.1 and L1.2 (similar to 40% a mino acid identity). Besides the high overall homology and conserved m odular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosop hila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/ra t ankyrin-binding glycoprotein), criteria characteristic of L1 were id entified with regard to the number of amino acids between positions of conserved:amino acid residues defining distances within-and between t wo adjacent Ig-like domains and FN-like repeats. These show a collinea rity in,the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these mod ules (designated the L1 family cassette), including the GPI-linked for ms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mou se PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cance r molecule (DCC), previously introduced as an N-CAM-like molecule, con forms to the L1 family cassette. Other structural features of CHL1 sha red between members of the L1 family are a high degree of N-glycosidic ally linked carbohydrates (similar to 20% of its molecular mass), whic h include the HNK-1 carbohydrate structure, and a pattern of protein f ragments comprising a major 185 kDa band and smaller fragments of 165 and 125 kDa. As for the other L1 family members, predominant expressio n of CHL1 is observed in the nervous system and at later developmental stages. In the central nervous system CHL1 is expressed by neurons, b ut, in contrast to L1, also by glial cells. Our findings suggest a com mon ancestral L1-like molecule which evolved via gene duplication to g enerate a diversity of structurally and functionally distinct yet simi lar molecules.