Characterization of an O-glycosylated plaque-associated protein from Alzheimer disease brain.
In this work we characterized a 90-kDa glycoprotein from Alzheimer disease (9OAzgp) brain extracts that is recognized by the GalNAc-specific lectin from Amaranthus leucocarpus (ALL), as determined through Western blot. The 90Azgp was purified by electro-elution, and its amino acid sequence determined from peptides obtained after trypsin digestion through MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight), and compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/2001) database. The 90Azgp showed 32% and 42% homology with the KIAA0310 protein from human brain and the human gastric mucin, respectively. Presence of O-glycosidically linked glycans in the proteins recognized by ALL was confirmed by inhibition of the lectin-glycoprotein interaction through hapten-inhibition assays and also by elimination of the O-glycosidically linked glycans after treatment with O-glycanase from Diplococcus pneumoniae. Electron transmission microscopy confirmed that the receptor recognized by the lectin is processed in the Golgi apparatus of AD neurons. Although the specific role of this glycoprotein has not been identified, considering that the presence of this lectin receptor co-localized with neuritic plaques and in AD sprouting neurons, it could suggest that the O-glycosyl-protein identified by the A. leucocarpus lectin participates in the pathogenesis of neurodegenerative diseases.
Espinosa
Blanca
B
Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
Guevara
Jorge
J
Hernández
Pedro
P
Slomianny
Marie-Christine
MC
Guzmán
Aida
A
Martínez-Cairo
Salvador
S
Zenteno
Edgar
E
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D000595:Amino Acid Sequence; D006023:Glycoproteins / Q000032:analysis* / Q000648:ultrastructure; D006031:Glycosylation; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D008970:Molecular Weight; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure
D006023:Glycoproteins