Amyloid precursor-like protein 2 (APLP2) is modified by the addition of chondroitin sulfate glycosaminoglycan at a single site.
beta-Amyloid, the principal component of senile plaques in individuals with Alzheimer's disease, is derived from larger integral membrane glycoproteins, termed amyloid precursor proteins (APP). APP is a member of a family of proteins that includes the amyloid precursor-like proteins APLP1 and APLP2. The present study examines the metabolism of mouse APLP2 in cultured mammalian cells. We report that in stably transfected Chinese hamster ovary and transiently transfected African green monkey kidney (COS-1) cells, APLP2 is modified by glycosaminoglycan (GAG) addition. The sensitivity of GAG-modified APLP2 to digestion with chondroitinase AC indicates that chondroitin sulfate (CS) chains are the preponderant GAG on APLP2. CS GAG modification of APLP2 occurs in a region with little homology to APP. Contained within this heterologous region is a predicted CS modification site, ENEGSGMAEQ (APLP2 residues 610-619); APLP2 polypeptides harboring a serine-to-alanine substitution at position 614 fail to undergo CS GAG modification. Our observation that APLP2 is modified by a pathway distinct from APP suggests that the two molecules may be functionally divergent.
Thinakaran
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Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
Sisodia
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D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000378:metabolism; D006224:Cricetinae; D006025:Glycosaminoglycans / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense; D011499:Protein Processing, Post-Translational; D014162:Transfection
C489697:APLP1 protein, human; D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D006025:Glycosaminoglycans; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C038142:chondroitin sulfate glycosaminoglycan; D002809:Chondroitin Sulfates