J. Holm et al., STRUCTURAL FEATURES OF A CLOSE HOMOLOG OF L1 (CHL1) IN THE MOUSE - A NEW MEMBER OF THE L1 FAMILY OF NEURAL RECOGNITION MOLECULES, European journal of neuroscience, 8(8), 1996, pp. 1613-1629
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.