DEVELOPMENTAL-CHANGES IN TAU-PHOSPHORYLATION - FETAL-TAU IS TRANSIENTLY PHOSPHORYLATED IN A MANNER SIMILAR TO PAIRED HELICAL FILAMENT-TAU CHARACTERISTIC OF ALZHEIMERS-DISEASE

被引:177
作者
BRION, JP
SMITH, C
COUCK, AM
GALLO, JM
ANDERTON, BH
机构
[1] INST PSYCHIAT,DEPT NEUROSCI,LONDON SE5 8AF,ENGLAND
[2] INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND
基金
英国惠康基金;
关键词
PHF-TAU; DEVELOPMENT; PHOSPHORYLATION; FETAL-TAU; ALZHEIMERS DISEASE;
D O I
10.1111/j.1471-4159.1993.tb07444.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rat and human fetal brain tau were probed with a panel of monoclonal antibodies (tau-1, AT8, 8D8, RT97, SM131, SM134) that distinguish between paired helical filament (PHF)-tau of Alzheimer's disease and normal adult brain tau. These antibodies discriminate between normal and PHF-tau because their epitopes are phosphorylated in PHF-tau. Although only one molecular isoform of tau was shown to be expressed in fetal brain, two fetal tau species could be distinguished on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the slower migrating species was recognized by all of the PHF-tau-specific antibodies. Moreover, this immunoreactivity was shown to be phosphorylation dependent. Our observations suggest that the abnormal phosphorylation of tau in Alzheimer's disease may be the result of reactivation of pathways governing the phosphorylation of tau in the developing brain.
引用
收藏
页码:2071 / 2080
页数:10
相关论文
共 59 条
[1]   MONOCLONAL-ANTIBODIES SHOW THAT NEUROFIBRILLARY TANGLES AND NEUROFILAMENTS SHARE ANTIGENIC DETERMINANTS [J].
ANDERTON, BH ;
BREINBURG, D ;
DOWNES, MJ ;
GREEN, PJ ;
TOMLINSON, BE ;
ULRICH, J ;
WOOD, JN ;
KAHN, J .
NATURE, 1982, 298 (5869) :84-86
[2]  
BAUDIER J, 1987, J BIOL CHEM, V262, P17577
[3]   THE SWITCH OF TAU-PROTEIN TO AN ALZHEIMER-LIKE STATE INCLUDES THE PHOSPHORYLATION OF 2 SERINE PROLINE MOTIFS UPSTREAM OF THE MICROTUBULE BINDING REGION [J].
BIERNAT, J ;
MANDELKOW, EM ;
SCHROTER, C ;
LICHTENBERGKRAAG, B ;
STEINER, B ;
BERLING, B ;
MEYER, H ;
MERCKEN, M ;
VANDERMEEREN, A ;
GOEDERT, M ;
MANDELKOW, E .
EMBO JOURNAL, 1992, 11 (04) :1593-1597
[4]  
BINDER LI, 1985, J CELL BIOL, V101, P1371, DOI 10.1083/jcb.101.4.1371
[5]  
Brion J. P., 1985, ARCH BIOL BRUX, V95, P229
[6]   BOTH ADULT AND JUVENILE TAU MICROTUBULE-ASSOCIATED PROTEINS ARE AXON SPECIFIC IN THE DEVELOPING AND ADULT-RAT CEREBELLUM [J].
BRION, JP ;
GUILLEMINOT, J ;
COUCHIE, D ;
FLAMENTDURAND, J ;
NUNEZ, J .
NEUROSCIENCE, 1988, 25 (01) :139-146
[7]   A68 PROTEINS IN ALZHEIMERS-DISEASE ARE COMPOSED OF SEVERAL TAU ISOFORMS IN A PHOSPHORYLATED STATE WHICH AFFECTS THEIR ELECTROPHORETIC MOBILITIES [J].
BRION, JP ;
HANGER, DP ;
COUCK, AM ;
ANDERTON, BH .
BIOCHEMICAL JOURNAL, 1991, 279 :831-836
[8]   TAU IN ALZHEIMER NEUROFIBRILLARY TANGLES - N-TERMINAL AND C-TERMINAL REGIONS ARE DIFFERENTIALLY ASSOCIATED WITH PAIRED HELICAL FILAMENTS AND THE LOCATION OF A PUTATIVE ABNORMAL PHOSPHORYLATION SITE [J].
BRION, JP ;
HANGER, DP ;
BRUCE, MT ;
COUCK, AM ;
FLAMENTDURAND, J ;
ANDERTON, BH .
BIOCHEMICAL JOURNAL, 1991, 273 :127-133
[9]  
BRION JP, 1985, J SUBMICR CYTOL PATH, V17, P89
[10]  
BRION JP, 1992, J NEUROCHEM, V60, P1372