Naslov
Myelin-associated glycoprotein (siglec-4) expression is progressively and selectively decreased in the brains of mice lacking complex gangliosides.

Autori
Sun, Ji ; Shaper, Nancy L. ; Itonori, Saki ; Heffer-Lauc, Marija ; Sheikh, Kazim A. ; Schnaar, Ronald L.

Izvornik
Glycobiology (0959-6658) 14 (2004); 851-857

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Galgt1 / N-acetylgalactosaminyltransferase / GD1a / GT1b / MAG

Sažetak
Myelin-associated glycoprotein (MAG, Siglec-4) is a quantitatively minor membrane component expressed preferentially on the innermost myelin wrap, adjacent to the axon. It stabilizes myelinaxon interactions by binding to complementary ligands on the axolemma. MAG, a member of the Siglec family of sialic acid-binding lectins, binds specifically to gangliosides GD1a and GT1b, which are the major sialoglycoconjugates on mammalian axons. Mice with a disrupted Galgt1 gene lack UDP-GalNAc:GM3/GD3 N-acetylgalactosaminyltransferase (GM2/GD2 synthase), and fail to express complex brain gangliosides, including GD1a and GT1b, instead expressing a comparable amount of the simpler gangliosides GM3, GD3, and O-acetyl-GD3. Galgt1 null mice produce similar amounts of total myelin compared to wild type mice, but as the mice age, they exhibit axon degeneration and dysmyelination with accompanying motor behavioral deficits. Here we report that Galgt1 null mice display progressive and selective loss of MAG from the brain. At 1.5-months of age MAG expression was similar in Galgt1 null and wild type mice. However, by 6-months of age MAG was decreased approximately 60%, and at 12-months of age approximately 70% in Galgt1 null mice compared to wild type littermates. Expression of the major myelin proteins myelin basic protein and proteolipid protein was not reduced in Galgt1 null mice compared to wild type. MAG mRNA expression was the same in 12-month old Galgt1 null compared to wild type mice, an age at which MAG protein expression was markedly reduced. We conclude that the maintenance of MAG protein levels depends on the presence of complex gangliosides, perhaps due to enhanced stability when MAG, on myelin, binds to its complementary ligands, GD1a and GT1b, on the apposing axon surface.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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