title: The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles.
abstract: Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy. To better understand the pathological roles of MAP2 and Tau, we compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal dysfunction and neuritic abnormalities, despite the absence of detergent-insoluble aggregates in worm neurons. Biochemical analysis revealed that the expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to microtubules. Newly raised antibodies to MAP2 that effectively distinguished between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed that MAP2 was not involved in the growth process of neurofibrillary tangles in the AD brain. These results indicate that Tau and MAP2 have different fates in the inclusion formation and raise the possibility that MAP2 plays a significant role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates.
authors.affiliation: Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Ce
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miyasaka
authors.affiliation: Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hatsuta
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kage-Nakadai
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000235:genetics; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D016875:tau Proteins