O-glycosylation pattern of CD24 from mouse brain.
The cell adhesion molecule CD24 is a highly glycosylated glycoprotein that plays important roles in the central nervous system, the immune system and in tumor biology. Since CD24 comprises only a short protein core of approximately 30 amino acids and low conservation among species, it has been proposed that the functions of CD24 are mediated by its glycosylation pattern. Our present study provides evidence that interaction of CD24 with the cell adhesion molecule L1 is mediated by O-linked glycans carrying alpha2,3-linked sialic acid. Furthermore, de-N-glycosylated CD24 was shown to promote or inhibit neurite outgrowth of cerebellar neurons or dorsal root ganglion neurons, respectively, to the same extent as untreated CD24. Therefore, this study is focused on the structural elucidation of the chemically released, permethylated CD24 O-glycans by electrospray ionization ion trap mass spectrometry. Our analyses revealed the occurrence of a diverse mixture of mucin-type and O-mannosyl glycans carrying, in part, functionally relevant epitopes, such as 3-linked sialic acid, disialyl motifs, Le(X), sialyl-Le(X) or HNK-1 units. Hence, our data provide the basis for further studies on the contribution of carbohydrate determinants to CD24-mediated biological activities.
Bleckmann
Christina
C
Institute of Biochemistry, Faculty of Medicine, University of Giessen, D-35392 Giessen, Germany.
Geyer
Hildegard
H
Lieberoth
Annika
A
Splittstoesser
Frauke
F
Liu
Yan
Y
Feizi
Ten
T
Schachner
Melitta
M
Kleene
Ralf
R
Reinhold
Vernon
V
Geyer
Rudolf
R
D000818:Animals; D001921:Brain; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism*; D018959:CD57 Antigens / Q000276:immunology; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000276:immunology; D054794:Glycomics; D006031:Glycosylation; D008358:Mannose / Q000737:chemistry; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D013402:Sugar Alcohols / Q000378:metabolism
D051927:CD24 Antigen; D018959:CD57 Antigens; D000939:Epitopes; D039842:Neural Cell Adhesion Molecule L1; D011134:Polysaccharides; D013402:Sugar Alcohols; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D008358:Mannose; D010100:Oxygen