Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid precursor protein and its homologue, APLP2.
Alzheimer's disease is characterized by the presence of parenchymal and cerebrovascular deposits of beta-amyloid (A beta). A beta is derived from larger amyloid precursor proteins (APP), a member of a family of related polypeptides that includes amyloid precursor-like proteins, APLP1 and APLP2. APP and APLP2 isoforms are encoded by several alternatively spliced APP and APLP2 transcripts, respectively. We previously reported that the APLP2-751 isoform is modified by the addition of chondroitin sulfate glycosaminoglycan (CS GAG) at Ser-614. In this report, we demonstrate that the APLP2-763 isoform, which contains an insertion of 12 amino acids immediately N-terminal to Ser-614, is not modified by CS GAG. Finally, we demonstrate that like APLP2-751, APP isoforms that lack sequences encoded by exon 15 (L-APP) are also modified by CS GAG, whereas APP forms containing exon 15 are not. We suggest that CS GAG modification of a subset of APP and APLP2 isoforms represents a means of generating functional diversity for these polypeptides.
Thinakaran
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Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Slunt
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HH
Sisodia
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; C038142:chondroitin sulfate glycosaminoglycan; D002809:Chondroitin Sulfates