Appicans are secreted and cell-associated
chondroitin sulfate proteoglycans containing Alzheimer
amyloid precursor (APP) as their core
protein. Appicans are found in brain tissue, and in cell cultures their expression depends on both cell type and growth conditions. Here we report that the core
protein of appicans derives from an APP
mRNA lacking exon 15. Splicing out of this exon creates a new consensus sequence for the attachment of a
chondroitin sulfate chain in the resulting APP product. Transfection of C6
glioma or 293 kidney fibroblast cells with APP cDNAs containing exon 15 produced no
appican, while transfection with an APP
cDNA lacking this exon induced high levels of
appican production. Polymerase chain reactions indicated that
appican-producing cells contained an APP
mRNA species without exon 15, whereas cells without this
mRNA produced no
appican. Site-directed mutagenesis combined with immunoreactivity experiments showed that the
chondroitin sulfate chain is attached to a
serine residue 16
amino acids upstream of the amino terminus of the A beta sequence of APP. The attachment of a
glycosaminoglycan chain close to the A beta sequence of APP may affect the proteolytic processing of APP and production of A beta. The
proteoglycan nature of APP suggests that addition of the
chondroitin sulfate glycosaminoglycan is important for the implementation of the
biological function of these
proteins.