beta-Amyloid peptide induces formation of actin stress fibers through p38 mitogen-activated protein kinase.
Based on the critical role of actin in the maintenance of synaptic function, we examined whether expression of familial beta-amyloid precursor protein APP-V642I (IAPP) or mutant presenilin-1 L286V (mPS1) affects actin polymerization in rat septal neuronal cells. Expression of either IAPP or mPS1 but not wild-type amyloid precursor protein or presenilin-1induced formation of actin stress fibers in SN1 cells, a septal neuronal cell line. Treatment with beta-amyloid (Abeta) peptide also caused formation of actin stress fibers in SN1 cells and primary cultured hippocampal neurons. Treatment with a gamma-secretase inhibitor completely blocked formation of actin stress fibers, indicating that overproduction of Abeta peptide induces actin stress fibers. Because activation of the p38 mitogen-activated protein kinase (p38MAPK)-mitogen-associated protein kinase-associated protein kinase (MAPKAPK)-2-heat-shock protein 27 signaling pathway mediates actin polymerization, we explored whether Abeta peptide activates p38MAPK and MAPKAPK-2. Expression of IAPP or mPS1 induced activation of p38MAPK and MAPKAPK-2. Treatment with a p38MAPK inhibitor completely inhibited formation of actin stress fibers mediated by Abeta peptide, IAPP or mPS1. Moreover, treatment with a gamma-secretase inhibitor completely blocked activation of p38MAPK and MAPKAPK-2. In summary, our data suggest that overproduction of Abeta peptide induces formation of actin stress fibers through activation of the p38MAPK signaling pathway in septal neuronal cells.
Song
Cheng
C
Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Perides
George
G
Wang
Dechun
D
Liu
Ya Fang
YF
D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics; D019943:Amino Acid Substitution; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002460:Cell Line; D002478:Cells, Cultured; D010450:Endopeptidases / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018832:Molecular Chaperones; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053764:Presenilin-1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D022502:Stress Fibers / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D000199:Actins; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D053764:Presenilin-1; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C486113:Hsbp1 protein, mouse; C486114:Hspb1 protein, rat; C509282:Bace1 protein, mouse