Localization and developmental changes of tau protein kinase I/glycogen synthase kinase-3 beta in rat brain.
tau protein kinase I (TPKI) purified from bovine brain extract has been shown to phosphorylate tau and to form paired helical filament (PHF) epitopes and was found recently to be identical to glycogen synthase kinase -3 beta (GSK-3 beta). Before elucidating a role of TPKI/GSK-3 beta in PHF formation, it is necessary to investigate the normal function of the enzyme. To study the distribution and developmental changes of the enzyme, specific polyclonal antibodies were prepared against TPKI and GSK-3 alpha. Immunoblot analysis demonstrated that TPKI was nearly specifically localized in the brain of adult rats. The level of TPKI in the rat brain was high at gestational day 18, peaked on postnatal day 8, and then decreased rapidly to a low level, which was sustained up to 2 years. Immunohistochemistry indicated primarily neuronal localization of TPKI. Growing axons were stained most intensely in the developing cerebellum, but the immunoreactivity became restricted to the gray matter in the mature tissue. Parallel fibers had a high level of TPKI and also stained intensely for tau. These findings indicate that tau is one of the physiological substrates of TPKI and suggest that the enzyme plays an important role in the growth of axons during development of the brain.
Takahashi
M
M
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Tomizawa
K
K
Kato
R
R
Sato
K
K
Uchida
T
T
Fujita
S C
SC
Imahori
K
K
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D000918:Antibody Specificity; D001369:Axons / Q000737:chemistry; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000254:growth & development*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D000939:Epitopes; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase