Related Experiment Videos
Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration
S Tang1, R W Woodhall, Y J Shen
1Department of Biological Sciences, Hunter College of the City University of New York 10021, USA.
Abstract:
Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration when used as a substrate for growth. However, to be characterized definitively as inhibitory rather than nonpermissive, MAG must also inhibit axonal regeneration when presented in solution. Here, we show that soluble dMAG (extracellular domain only), released in abundance from myelin and found in vivo and chimeric MAG-Fc, can potently inhibit axonal regeneration. For both dMAG and MAG-Fc, inhibition is dose-dependent. If myelin-conditioned medium is immunodepleted of dMAG, or if a MAG antibody is included with MAG-Fc, inhibition is completely neutralized. Together with MAG's ability to induce growth cone collapse, these results demonstrate that MAG is an inhibitory molecule and not merely nonpermissive. The results also suggest that MAG binds to a specific receptor and initiates a signal transduction cascade to effect inhibition. Importantly, these results indicate that soluble dMAG detected in vivo could contribute to the lack of regeneration in the mammalian CNS after injury.
Insights
Soluble myelin-associated glycoprotein (MAG) potently inhibits axonal regeneration, confirming MAG is inhibitory. This finding is crucial for understanding central nervous system (CNS) repair after injury.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Myelin-associated glycoprotein (MAG) is known to inhibit axonal regeneration when presented as a growth substrate.
- Its role as a purely inhibitory molecule, rather than just nonpermissive, requires demonstration in soluble forms.
Purpose of the Study:
- To determine if soluble myelin-associated glycoprotein (dMAG) inhibits axonal regeneration.
- To confirm MAG's inhibitory nature and explore its mechanism and in vivo relevance.
Main Methods:
- Experiments using soluble dMAG and chimeric MAG-Fc proteins to assess axonal regeneration.
- Dose-dependency studies and neutralization assays with immunodepletion and antibodies.
- Evaluation of MAG's effect on growth cone collapse.
Main Results:
- Soluble dMAG and MAG-Fc potently inhibit axonal regeneration in a dose-dependent manner.
- Inhibition is neutralized by removing dMAG from myelin-conditioned medium or using MAG antibodies.
- MAG's ability to induce growth cone collapse further supports its inhibitory role.
Conclusions:
- Myelin-associated glycoprotein (MAG) is definitively an inhibitory molecule, not merely nonpermissive.
- MAG likely acts via a specific receptor and signal transduction pathway.
- Soluble MAG in vivo may significantly impede mammalian central nervous system (CNS) regeneration after injury.