title: Rapid changes in phospho-MAP/tau epitopes during neuronal stress: cofilin-actin rods primarily recruit microtubule binding domain epitopes.
abstract: Abnormal mitochondrial function is a widely reported contributor to neurodegenerative disease including Alzheimer's disease (AD), however, a mechanistic link between mitochondrial dysfunction and the initiation of neuropathology remains elusive. In AD, one of the earliest hallmark pathologies is neuropil threads comprising accumulated hyperphosphorylated microtubule-associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its associated protein cofilin (AC rods) also occur in AD. Using a series of antibodies--AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422--raised against different phosphoepitopes on tau, we characterize the pattern of expression and re-distribution in neurites of these phosphoepitope labels during mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate that epitopes recognized by the monoclonal antibody 12E8, are the only species rapidly recruited into AC rods. These results were recapitulated with the actin depolymerizing drug Latrunculin B, which induces AC rods and a concomitant increase in the 12E8 signal measured on Western blot. This suggests that AC rods may be one way in which MAP redistribution and phosphorylation is influenced in neurons during mitochondrial stress and potentially in the early pathogenesis of AD.
authors: The Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors: Ineka T
authors: IT
authors: Whiteman
authors: Laurie S
authors: LS
authors: Minamide
authors: De Lian
authors: de L
authors: Goh
authors: James R
authors: JR
authors: Bamburg
authors: Claire
authors: C
authors: Goldsbury
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D000939:Epitopes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D000939:Epitopes; D016875:tau Proteins