Abeta1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases.
A number of psychiatric and neurodegenerative disorders, such as Alzheimer's disease, are characterized by abnormalities in the neuronal cytoskeleton. Here, we find that the enhancement in actin polymerization induced by fibrillar amyloid-beta peptide (Abeta) is associated with increased activity of Rac1/Cdc42 Rho GTPases. Rac1 upregulation involves the participation of Tiam1, a Rac guanine-nucleotide exchange factor, where Abeta exposure leads to Tiam1 activation by a Ca(2+)-dependent mechanism. These results point to Rho GTPases as one of the targets in Abeta-induced neurodegeneration in Alzheimer's disease pathology, with a role in mediating changes in the actin cytoskeletal dynamics.
Mendoza-Naranjo
Ariadna
A
Laboratory of Cellular, Molecular Biology and Neuroscience, Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Nunoa, Santiago, Chile. amendoza@med.uchile.cl
Gonzalez-Billault
Christian
C
Maccioni
Ricardo B
RB
D000199:Actins / Q000032:analysis / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010590:Phalloidine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines; D013347:Subcellular Fractions; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D016229:Amyloid beta-Peptides; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D012235:Rhodamines; C098994:amyloid beta-protein (1-43); D010590:Phalloidine; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins