Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth.
Although carbohydrates have been implicated in cell interactions in the nervous system, the molecular bases of their functions have remained largely obscure. Here, we show that promotion or inhibition of neurite outgrowth of cerebellar or dorsal root ganglion neurons, respectively, induced by the mucin-type adhesion molecule CD24 depends on alpha2,3-linked sialic acid and Lewis(x) present on glia-specific CD24 glycoforms. Alpha2,3-sialyl residues of CD24 bind to a structural motif in the first fibronectin type III domain of the adhesion molecule L1. Following the observation that the adhesion molecules TAG-1 and Contactin show sequence homologies with fucose-specific lectins, we obtained evidence that TAG-1 and Contactin mediate Lewis(x)-dependent CD24-induced effects on neurite outgrowth. Thus, L1, TAG-1, and Contactin function as lectin-like neuronal receptors. Their cis interactions with neighboring adhesion molecules, e.g., Caspr1 and Caspr2, and with their triggered signal transduction pathways elicit cell type-specific promotion or inhibition of neurite outgrowth induced by glial CD24 in a glycan-dependent trans interaction.
Lieberoth
Annika
A
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
Splittstoesser
Frauke
F
Katagihallimath
Nainesh
N
Jakovcevski
Igor
I
Loers
Gabriele
G
Ranscht
Barbara
B
Karagogeos
Domna
D
Schachner
Melitta
M
Kleene
Ralf
R
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000187:drug effects; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D058969:Contactin 2; D058966:Contactins; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D006031:Glycosylation / Q000187:drug effects; D047468:Immunoprecipitation / Q000379:methods; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D016256:Lewis X Antigen / Q000494:pharmacology*; D008124:Locomotion / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020127:Recovery of Function / Q000235:genetics; D012794:Sialic Acids / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014162:Transfection / Q000379:methods
D051927:CD24 Antigen; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; C491322:Cntnap1 protein, mouse; D058969:Contactin 2; D058966:Contactins; D039841:Leukocyte L1 Antigen Complex; D016256:Lewis X Antigen; D010455:Peptides; D012794:Sialic Acids