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Involvement of glycogen synthase kinase‐3β and tau phosphorylation in neuronal Golgi disassembly
Author(s) -
Elyaman Wassim,
Yardin Catherine,
Hugon Jacques
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00838.x
Subject(s) - golgi apparatus , phosphorylation , microbiology and biotechnology , gsk 3 , biology , brefeldin a , kinase , protein kinase a , biochemistry , chemistry , endoplasmic reticulum
The dissociation of the neuronal Golgi complex is a classical feature observed in neurodegenerative disorders including Alzheimer's disease. The goal of this study is to determine if the phosphorylation of tau protein is involved in neuronal Golgi disassembly. Primary cortical cultures were exposed to two Golgi toxins, brefeldin A (BFA) or nordihydroguaiaretic acid (NDGA). Immunocytochemical studies using the anti58 k antibody revealed that Golgi disassembly started in exposed neurons a few minutes after treatment. BFA and NDGA induced a rapid and transient increase in tau phosphorylation in a site‐specific manner on immunoblots. In addition, the increase in tau phosphorylation directly correlated with a transient dissociation of tau from the cytoskeleton and a decrease of the acetylated tubulin. Furthermore, the activity of glycogen synthase kinase‐3β (GSK‐3β) increased transiently, as demonstrated by the kinase activity assay and by immunoblottings of serine‐9 and tyrosine‐216 phosphorylated of GSK‐3β. A decrease of the Akt phosphorylated form was also shown. The increase in tau phosphorylation was inhibited by the GSK‐3β inhibitor, lithium. Finally, morphometric studies showed that lithium partially blocked the Golgi disassembly caused by BFA or NDGA. Together these findings indicate that GSK‐3β activity and tau phosphorylation state are involved in the maintenance of the neuronal Golgi organization.