Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth.
Contact-dependent axon growth inhibitory activity is present in CNS myelin, but the inhibitory proteins have not been fully characterized. We report here that at least two peaks of inhibitory activity can be separated by fractionating solubilized CNS myelin proteins by DEAE chromatography. A major peak of inhibitory activity corresponded to the elution profile of myelin-associated glycoprotein (MAG). Immunodepletion of MAG from these inhibitory fractions removed neurite growth inhibition, whereas recombinant MAG (ectodomain) was a potent inhibitor of neurite outgrowth. Immunodepletion of MAG from total extracts of CNS myelin restored neurite growth up to 63% of control levels. These results establish that MAG is a significant, and possibly the major, inhibitor in CNS myelin; this has broad implications for axonal regeneration in the injured mammalian CNS.
McKerracher
L
L
Center for Research in Neuroscience, Montreal General Hospital Research Institute, Quebec, Canada.
David
S
S
Jackson
D L
DL
Kottis
V
V
Dunn
R J
RJ
Braun
P E
PE
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002852:Chromatography, Ion Exchange; D006358:Hot Temperature; D007163:Immunosorbent Techniques; D009046:Motor Neurons / Q000648:ultrastructure; D009185:Myelin Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D011994:Recombinant Proteins