Volume 270,
Number 18,
Issue of May 5, pp. 10388-10391, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
The
Chondroitin Sulfate Attachment Site of Appican Is Formed by Splicing
Out Exon 15 of the Amyloid Precursor Gene
Menelas N.
Pangalos
,
Spiros
Efthimiopoulos
,
Junichi
Shioi
,
Nikolaos K.
Robakis
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
sequence of APP. The
attachment of a glycosaminoglycan chain close to the A sequence of
APP may affect the proteolytic processing of APP and production of
A. 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.
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