Metabolism of the amyloid precursor-like protein 2 in MDCK cells. Polarized trafficking occurs independent of the chondroitin sulfate glycosaminoglycan chain.
Deposition of beta-amyloid peptide in senile plaques is a principal neuropathological hallmark of Alzheimer's disease. beta-Amyloid peptide is derived from larger amyloid precursor proteins. Amyloid precursor protein is a member of a family of integral membrane glycoproteins that includes amyloid precursor-like protein (APLP) 1 and 2. Alternatively spliced pre-mRNAs encode several APLP2 isoforms; the APLP2-751 isoform is a substrate for modifications by a chondroitin sulfate glycosaminoglycan (CS GAG) chain, whereas the APLP2-763 isoform does not undergo CS GAG modification. In this report, we have examined the sorting and metabolism of APLP2-751 and APLP2-763 in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate that, despite differences in post-translational modifications, both the APLP2-751 proteoglycan and APLP2-763 isoform were targeted and secreted to the basolateral compartment of MDCK cells. We document that the kinetics of intracellular maturation of full-length forms and secretion of soluble derivatives generated from each isoform were indistinguishable. Our results are consistent with the view that, in MDCK cells, the CS GAG chain of APLP2 has little influence on intracellular trafficking and that the principal basolateral targeting determinants are likely to reside in the APLP2 core protein.
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Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Thinakaran
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Sisodia
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation; D016764:Cell Polarity; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D004285:Dogs; D006025:Glycosaminoglycans / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism
C489697:APLP1 protein, human; D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; C492952:Aplp2 protein, mouse; D006025:Glycosaminoglycans; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D002809:Chondroitin Sulfates