Chondroitin sulfate proteoglycan form of the Alzheimer's beta-amyloid precursor.
The Alzheimer's amyloid beta protein is derived from a family of membrane glycoproteins termed amyloid precursor proteins (APP). Here we show that APP exists as the core protein of a chondroitin sulfate (CS) proteoglycan, ranging in apparent molecular size from 140 to 250 kDa, secreted by glial cell line C6. After partial purification on ion-exchange and gel chromatography, the secreted APP proteoglycan was recognized on Western blots by several antibodies specific to different regions of APP. Chondroitinase AC or ABC treatment of our samples completely eliminated the high molecular weight proteoglycan with a concomitant increase in the APP protein. This digested product reacted with an anti-stub antibody which recognizes 4-sulfated disaccharide. Sequencing of the N terminus of the core protein of this CS proteoglycan yielded 18 residues identical to the N terminus sequence of the mature APP. Quantitative analysis showed that, in this cell line, about 90% of the secreted nexin II form of APP occurs in the proteoglycan form, suggesting that the CS chains have a role in the biological function of this protein. The close proximity of two consensus CS attachment sites to both the N terminus of the amyloid beta protein and the secretase cleavage site, suggests that the CS chains may affect the proteolysis of APP and production of the amyloid beta protein.
Shioi
J
J
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
Anderson
J P
JP
Ripellino
J A
JA
Robakis
N K
NK
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000302:isolation & purification*; D000818:Animals; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry* / Q000302:isolation & purification; D002810:Chondroitinases and Chondroitin Lyases; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009457:Neuroglia; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D011508:Chondroitin Sulfate Proteoglycans; D010446:Peptide Fragments; D002810:Chondroitinases and Chondroitin Lyases