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Aggregation of Neurofilaments in NF‐L Transfected Neuronal Cells: Regeneration of the Filamentous Network by a Protein Kinase C Inhibitor
Author(s) -
Carter J. E.,
Gallo J.M.,
Anderson V. E. R.,
Anderton B. H.,
Robertson J.
Publication year - 1996
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.1471-4159.1996.67051997.x
Subject(s) - neurofilament , regeneration (biology) , transfection , microbiology and biotechnology , kinase , chemistry , protein kinase c , biology , biochemistry , gene , immunology , immunohistochemistry
Cytoplasmic inclusion bodies that are accumulations of neurofilaments are the pathological hallmark of many neurodegenerative diseases and have been produced in transgenic mice by overexpression of mouse (NF‐L and NF‐M; light and medium chains, respectively) and human (NF‐M and NF‐H; medium and heavy chains, respectively) neurofilament subunits. This report describes a neuronal culture model in which human NF‐L was overexpressed to produce cytoplasmic accumulations of neurofilaments within cell bodies concomitant with the collapse of the endogenous neurofilament network. Electron microscopy showed that, within accumulations, neurofilaments retained a filamentous structure. The culture model thus provides a novel system in which the effect on neurofilament accumulations of manipulating protein phosphorylation can be studied. Treatment of cells containing neurofilament accumulations with bisindolylmaleimide, a specific protein kinase C inhibitor, resulted in regeneration of the filamentous network; this effect was not due to a change in the level of transfected NF‐L expression. These findings lend support to the suggestion that an impairment in the regulation of protein phosphorylation may lead to the accumulation of neurofilaments seen in neurodegenerative disease.