Related Experiment Videos
Regulation of myelin basic protein phosphorylation by mitogen-activated protein kinase during increased action
C M Atkins1, M Yon, N P Groome
1Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
Insights
Neuronal activity regulates myelin basic protein (MBP) phosphorylation via mitogen-activated protein kinase (MAPK) in the hippocampus. This process requires action potentials, calcium, and involves nitric oxide and reactive oxygen species.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Myelin basic protein (MBP) phosphorylation is crucial for myelin sheath stability.
- Mitogen-activated protein kinase (MAPK) influences MBP phosphorylation during development and in multiple sclerosis.
Purpose of the Study:
- To investigate the physiological regulation of MBP phosphorylation by MAPK in response to neuronal activity.
- To explore the signaling pathways involved in MBP phosphorylation in the hippocampal alveus.
Main Methods:
- Utilized a phosphospecific antibody for MBP Thr95 phosphorylation.
- Applied high-frequency and low-frequency stimulation to the alveus.
- Used tetrodotoxin, reactive oxygen species scavengers, nitric oxide synthase inhibitor, and calcium removal.
Main Results:
- High-frequency stimulation significantly increased MBP phosphorylation, while low-frequency stimulation did not.
- MBP phosphorylation changes were dependent on action potential propagation.
- The observed changes were modulated by calcium, nitric oxide, and reactive oxygen species.
Conclusions:
- Neuronal activity regulates MBP phosphorylation through a MAPK-dependent pathway in the alveus.
- Calcium influx triggers axonal nitric oxide synthase, leading to nitric oxide and superoxide production, which in turn regulate MBP phosphorylation.
- This mechanism highlights a novel link between neuronal activity and myelin regulation.