Regulation of myelin basic protein phosphorylation by mitogen-activated protein kinase during increased action potential firing in the hippocampus

Coleen M Atkins, M. Yon, N. P. Groome, J. David Sweatt

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Myelin basic protein (MBP) phosphorylation is a complex regulatory process that modulates the contribution of MBP to the stability of the myelin sheath. Recent research has demonstrated the modulation of MBP phosphorylation by mitogen-activated protein kinase (MAPK) during myelinogenesis and in the demyelinating disease multiple sclerosis. Here we investigated the physiological regulation of MBP phosphorylation by MAPK during neuronal activity in the alveus, the myelinated output fibers of the hippocampus. Using a phosphospecific antibody that recognizes the predominant MAPK phosphorylation site in MBP, Thr95, we found that MBP phosphorylation is regulated by high-frequency stimulation but not low-frequency stimulation of the alveus. This change was blocked by application of tetrodotoxin, indicating that action potential propagation in axons is required. It is interesting that the change in MBP phosphorylation was attenuated by the reactive oxygen species scavengers superoxide dismutase and catalase and the nitric oxide synthase inhibitor N-nitro-L-arginine. Removal of extracellular calcium also blocked the changes in MBP phosphorylation. Thus, we propose that during periods of increased neuronal activity, calcium activates axonal nitric oxide synthase, which generates the intercellular messengers nitric oxide and superoxide and regulates the phosphorylation state of MBP by MAPK.

Original languageEnglish
Pages (from-to)1090-1097
Number of pages8
JournalJournal of Neurochemistry
Volume73
Issue number3
DOIs
StatePublished - Aug 30 1999
Externally publishedYes

Fingerprint

Phosphorylation
Myelin Basic Protein
Mitogen-Activated Protein Kinases
Action Potentials
Hippocampus
Nitric Oxide Synthase
Phospho-Specific Antibodies
Calcium
Protein Stability
Tetrodotoxin
Demyelinating Diseases
Myelin Sheath
Superoxides
Catalase
Superoxide Dismutase
Multiple Sclerosis
Axons
Arginine
Reactive Oxygen Species
Nitric Oxide

Keywords

  • Action potential
  • Alveus
  • Hippocampus
  • Mitogen-activated protein kinase
  • Myelin basic protein
  • Phosphorylation
  • Reactive nitrogen species
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Regulation of myelin basic protein phosphorylation by mitogen-activated protein kinase during increased action potential firing in the hippocampus. / Atkins, Coleen M; Yon, M.; Groome, N. P.; Sweatt, J. David.

In: Journal of Neurochemistry, Vol. 73, No. 3, 30.08.1999, p. 1090-1097.

Research output: Contribution to journalArticle

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