Secretion and differential localization of the proteolytic cleavage products Abeta40 and Abeta42 of the Alzheimer amyloid precursor protein in human fetal myogenic cells.
Abeta peptides are major components of the amyloid plaques that characterize Alzheimer's disease. These peptides are proteolytic cleavage products of the amyloid precursor protein (APP) and are generated by beta- and gamma-secretases. Here we show by multiparameter immunofluorescence imaging in muscle cells that localization of the Abeta40 and Abeta42 cleavage products reveals different myocyte types in a three-dimensional culture system. These myocyte types are heterogeneous by selective intracellular concentration of either Abeta40 or Abeta42 in vesicular structures, whilst only the Abeta40 peptide is secreted as indicated by Western blot analysis. This cellular pattern of APP proteolysis and Abeta peptide secretion correlates with lack of L-APP mRNA splice isoforms. Differential secretion and intracellular accumulation of Abeta peptides is characteristic for the early myocyte development and might be related to cell fusion.
Haars
R
R
Institute of Medical Neurobiology, Molecular Pattern Recognition and Neuroimmunology Research Group, Otto-von-Guericke-University, Magdeburg, Germany.
Schneider
A
A
Bode
M
M
Schubert
W
W
D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology; D011233:Precipitin Tests; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D020033:Protein Isoforms; D012313:RNA; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D016650:Fluorescein-5-isothiocyanate