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Involvement of mature tau isoforms in the stabilization of neurites in PC12 cells
Author(s) -
Hanemaaijer R.,
Ginzburg I.
Publication year - 1991
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490300117
Subject(s) - neurite , gene isoform , microtubule , microbiology and biotechnology , nerve growth factor , tau protein , in vivo , biology , tubulin , microtubule associated protein , messenger rna , rnase p , chemistry , in vitro , rna , biochemistry , medicine , genetics , gene , receptor , disease , alzheimer's disease
Tau microtubule—associated proteins are believed to play a role in regulation of the growth of neuronal processes. In order to study the function of tau protein in vivo, we examined the inhibition of tau expression in PC12 cells by exposing the cells to tau antisense oligodeoxynucleotides. A speceific retraction of neurites was observed after 3–4 days of incubation with nerve growth factor (NGF) and the antisense oligodeoxynucleotides. This is different from the previously described retraction of neurites at the initiation step following exposure to tubulin antisense oligodeoxynucleotides, indicating that tau proteins are involved at later stages of neurite outgrowth. Analysis of tau protein isoforms in NGF‐induced PC12 cells showed a transition from immature to mature tau isoforms, thus relating the appearance of the latter with the stabilization step of neurite outgrowth. Use of an RNase‐protection assay demonstrated a similar switch from immature to mature tau mRNA species. The transition to stable microtubules was verified by the appearance of microtubule bundles and their stability to colchicine treatment. Both phenomena occurred between 2 and 4 days of NGF induction. These results indicate that in vivo only mature tau isoforms are involved in the transition from unstable to stable neurites, which is a key step in neuronal development.