Modulation of phosphorylation of neuronal cytoskeletal proteins by neuronal depolarization.
1. The neuronal cytoskeletal protein tau and the carboxy tails of cytoskeletal proteins neurofilament-M (NF-M) and neurofilament-H (NF-H) are phosphorylated on serine residues by the cyclin-dependent kinase cdk-5. 2. In aggregating neuronal-glial cultures we show that veratridine-mediated cation influx causes dephosphorylation of tau, NF-M and NF-H. Dephosphorylation was blocked specifically by cyclosporine A but not by okadiac acid at concentrations up to 200 nM. 3. These results suggest that veratridine-triggered cation influx causes activation of PP-2B (calcineurin) leading to dephosphorylation of these cytoskeletal proteins.
Mata
M
M
Department of Neurology, University of Pittsburgh, Pennsylvania, USA.
Honegger
P
P
Fink
D J
DJ
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009467:Neuromuscular Depolarizing Agents; D016875:tau Proteins; D014701:Veratridine; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases