Phosphorylation of tau by glycogen synthase kinase 3 beta affects the ability of tau to promote microtubule self-assembly

被引:82
作者
Utton, MA
Vandecandelaere, A
Wagner, U
Reynolds, CH
Gibb, GM
Miller, CCJ
Bayley, PM
Anderton, BH
机构
[1] INST PSYCHIAT,DEPT NEUROSCI,LONDON SE5 8AF,ENGLAND
[2] NATL INST MED RES,DEPT PHYS BIOCHEMN,LONDON NW7 1AA,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1042/bj3230741
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
To study the effects of phosphorylation by glycogen synthase kinase-3 beta (GSK-3 beta) on the ability of the microtubule-associated protein tau to promote microtubule self-assembly, tau isoform 1 (foetal tau) and three mutant forms of this tau isoform were investigated. The three mutant forms of tau had the following serine residues, known to be phosphorylated by GSK-3, replaced with alanine residues so as to preclude their phosphorylation: (1) Ser-199 and Ser-202 (Ser-199/202 --> Ala), (2) Ser-235 (Ser-235 --> Ala) and (3) Ser-396 and Ser-404 (Ser-396/404 --> Ala). Wild-type tau and the mutant forms of tau were phosphorylated with GSK-3 beta, and their ability to promote microtubule self-assembly was compared with the corresponding non-phosphorylated tau species. In the non-phosphorylated form, wild-type tau and all of the mutants affected the mean microtubule length and number concentrations of assembled microtubules in a manner consistant with enhanced microtubule nucleation. Phosphorylation of these tau species with GSK-3 beta consistently reduced the ability of a given tau species to promote microtubule self-assembly, although the affinity of the tau for the microtubules was not greatly affected by phosphorylation since the tau species remained largely associated with the microtubules. This suggests that the regulation of microtubule assembly can be controlled by phosphorylation of tau at sites accessible to GSK-3 beta by a mechanism that does not necessarily involve the dissociation of tau from the microtubules.
引用
收藏
页码:741 / 747
页数:7
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