Characterization of appican, the chondroitin sulfate proteoglycan form of the Alzheimer amyloid precursor protein.
In this report we focus on the characterization of appican, the chondroitin sulfate proteoglycan form of amyloid precursor protein (APP), and the role that it and other proteoglycans may play in AD. Appican is expressed by certain transformed cell lines of neural origin, namely C6 cells and N2a neuroblastomas. It is detected in both human and rat brain and in primary cultures is expressed by astrocytes, but not neurons. The core protein of appican has been shown to be an alternatively spliced isoform of APP, lacking exon 15 of the APP gene, originally identified in leukocytes (L-APP). Splicing out of exon 15 results in the joining of exons 14 and 16, and formation of an Asp-Xaa-Ser-Gly consensus sequence for chondroitin sulfate chain attachment to serine 619 of L-APP, which lies 16 amino acids upstream of the A beta peptide sequence. Mutation of this serine residue to an alanine prevented chondroitin sulfate chain addition to the core protein. Levels of appican expression could be regulated by growth conditions independently of APP, suggesting that these molecules may serve distinct physiological roles within the cell. Morphological changes were also observed in both astrocytic and transformed cell cultures, that appeared to reflect changes in levels of appican expression. Preliminary data suggest that appican may be a strong cell adhesion molecule. Transfected C6 glioma cells overexpressing appican remained attached to tissue culture dishes markedly better than either C6 cells over-expressing exon-15 containing APP or WT C6 cells. Appican-enriched extracellular matrix (ECM) was also observed to serve as a much better substrate for attachment of N2a neuroblastomas, pheocromocytoma PC12 cells and primary astrocytes compared to APP enriched ECM.
Pangalos
M N
MN
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Shioi
J
J
Efthimiopoulos
S
S
Wu
A
A
Robakis
N K
NK
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000378:metabolism / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D011508:Chondroitin Sulfate Proteoglycans; D011509:Proteoglycans; C093487:appican; D002809:Chondroitin Sulfates