Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease

American Association for the Advancement of Science (AAAS) - Tập 235 Số 4796 - Trang 1641-1644 - 1987
Hajime Mori1, Jun Kondo2, Yasuo Ihara1
1Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173 Japan
2Mitsubishi Chemical Industries Limited Research Center, Biosciences Laboratory, Kamoshida, Midori- ku, Yokohama 227, Japan.

Tóm tắt

Paired helical filaments (PHF), which constitute a distinct type of pathological neuronal fiber, are the principal constituent of neurofibrillary tangles that occur in the brain of patients with Alzheimer's disease. Their insolubility in sodium dodecyl sulfate and urea has prevented the analysis of their subunit composition by gel electrophoresis. A monoclonal antibody (DF2) was isolated that specifically labeled PHF at both the light and electron microscopic levels. It labeled a small polypeptide (5 kilodaltons) that was shown to be ubiquitin in immunoblots of the soluble fraction of brain homogenates. To obtain direct evidence that ubiquitin is a component of PHF, PHF were treated with concentrated formic acid and digested with lysylendopeptidase; ubiquitin-derived peptides were then identified by reversed-phase high-performance liquid chromatography. Two fragments in the PHF digest were identified as derived from ubiquitin by protein sequencing. This procedure should make possible definitive identification of other PHF components.

Từ khóa


Tài liệu tham khảo

10.1126/science.3083508

Brion J. P. paper presented at the International Tropon-Bayer-Symposium "Aging of the brain " Cologne F.R.G. 13 to 16 November (1984).

FINLEY, D, THERMOLABILITY OF UBIQUITIN-ACTIVATING ENZYME FROM THE MAMMALIAN-CELL CYCLE MUTANT TS85, CELL 37: 43 (1984).

GOLDSTEIN, G, ISOLATION OF A POLYPEPTIDE THAT HAS LYMPHOCYTE-DIFFERENTIATING PROPERTIES AND IS PROBABLY REPRESENTED UNIVERSALLY IN LIVING CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 72: 11 (1975).

GRUNDKEIQBAL, I, MICROTUBULE-ASSOCIATED PROTEIN-TAU - A COMPONENT OF ALZHEIMER PAIRED HELICAL FILAMENTS, JOURNAL OF BIOLOGICAL CHEMISTRY 261: 6084 (1986).

GRUNDKEIQBAL, I, ABNORMAL PHOSPHORYLATION OF THE MICROTUBULE-ASSOCIATED PROTEIN-TAU (TAU) IN ALZHEIMER CYTOSKELETAL PATHOLOGY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 4913 (1986).

HAAS, A.L., THE IMMUNOCHEMICAL DETECTION AND QUANTITATION OF INTRACELLULAR UBIQUITIN-PROTEIN CONJUGATES, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 2464 (1985).

HAAS, A.L., HEMIN INHIBITS ATP-DEPENDENT UBIQUITIN-DEPENDENT PROTEOLYSIS - ROLE OF HEMIN IN REGULATING UBIQUITIN CONJUGATE DEGRADATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 78: 6845 (1981).

HAAS, A.L., THE LARGE-SCALE PURIFICATION OF UBIQUITIN FROM HUMAN-ERYTHROCYTES, PREPARATIVE BIOCHEMISTRY 15: 49 (1985).

HERSHKO, A, COMPONENTS OF UBIQUITIN-PROTEIN LIGASE SYSTEM - RESOLUTION, AFFINITY PURIFICATION, AND ROLE IN PROTEIN BREAKDOWN, JOURNAL OF BIOLOGICAL CHEMISTRY 258: 8206 (1983).

HERSHKO, A, PROPOSED ROLE OF ATP IN PROTEIN BREAKDOWN - CONJUGATION OF PROTEINS WITH MULTIPLE CHAINS OF THE POLYPEPTIDE OF ATP-DEPENDENT PROTEOLYSIS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 77: 1783 (1980).

HIROMI, Y, ACTIN GENE-MUTATIONS IN DROSOPHILA - HEAT-SHOCK ACTIVATION IN THE INDIRECT FLIGHT MUSCLES, EMBO JOURNAL 4: 1681 (1985).

IHARA, Y, PHOSPHORYLATED TAU PROTEIN IS INTEGRATED INTO PAIRED HELICAL FILAMENTS IN ALZHEIMERS-DISEASE, JOURNAL OF BIOCHEMISTRY 99: 1807 (1986).

IHARA, Y, ANTIBODIES TO PAIRED HELICAL FILAMENTS IN ALZHEIMERS-DISEASE DO NOT RECOGNIZE NORMAL BRAIN PROTEINS, NATURE 304: 727 (1983).

KARLIK, C.C., A NONSENSE MUTATION WITHIN THE ACT88F ACTIN GENE DISRUPTS MYOFIBRIL FORMATION IN DROSOPHILA INDIRECT FLIGHT MUSCLES, CELL 38: 711 (1984).

KIDD, M, PAIRED HELICAL FILAMENTS IN ELECTRON MICROSCOPY OF ALZHEIMERS DISEASE, NATURE 197: 192 (1963).

KOSIK, K.S., MICROTUBULE-ASSOCIATED PROTEIN TAU (TAU) IS A MAJOR ANTIGENIC COMPONENT OF PAIRED HELICAL FILAMENTS IN ALZHEIMER-DISEASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 4044 (1986).

MASAKI, T, STUDIES ON A NEW PROTEOLYTIC-ENZYME FROM ACHROMOBACTER-LYTICUS M497-1 .1. PURIFICATION AND SOME ENZYMATIC-PROPERTIES, BIOCHIMICA ET BIOPHYSICA ACTA 660: 44 (1981).

MASAKI, T, STUDIES ON A NEW PROEOLYTIC ENZYME FROM ACHROMOBACTER-LYTICUS M497-1 .2. SPECIFICITY AND INHIBITION STUDIES OF ACHROMOBACTER PROTEASE-I, BIOCHIMICA ET BIOPHYSICA ACTA 660: 51 (1981).

MASAKI, T, JOURNAL OF THE AGRICULTURAL CHEMICAL SOCIETY OF JAPAN 58: 865 (1984).

MORI H unpublished data.

MUNRO, S, MOLECULAR-GENETICS - WHAT TURNS ON HEAT-SHOCK GENES, NATURE 317: 477 (1985).

NUKINA, N, ONE OF THE ANTIGENIC DETERMINANTS OF PAIRED HELICAL FILAMENTS IS RELATED TO TAU PROTEIN, JOURNAL OF BIOCHEMISTRY 99: 1541 (1986).

SCHLESINGER, D.H., COMPLETE AMINO-ACID SEQUENCE OF UBIQUITIN, AN ADENYLATE CYCLASE STIMULATING POLYPEPTIDE PROBABLY UNIVERSAL IN LIVING CELLS, BIOCHEMISTRY 14: 2214 (1975).

SELKOE, D, BANBURY REPORT 15: 125 (1983).

10.1126/science.6120571

10.1016/0022-510X(70)90063-8

WILCOCK, G.K., PLAQUES, TANGLES AND DEMENTIA - A QUANTITATIVE STUDY, JOURNAL OF THE NEUROLOGICAL SCIENCES 56: 343 (1982).

WISNIEWSKI, H.M., NEUROFIBRILLARY TANGLES OF PAIRED HELICAL FILAMENTS, JOURNAL OF THE NEUROLOGICAL SCIENCES 27: 173 (1976).

WOOD, J.G., NEUROFIBRILLARY TANGLES OF ALZHEIMER-DISEASE SHARE ANTIGENIC DETERMINANTS WITH THE AXONAL MICROTUBULE-ASSOCIATED PROTEIN TAU (TAU), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 4040 (1986).

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 235 Số 4796

1641-1644

Thông tin tác giả