Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor
Science, 2002•science.org
Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in
myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has
been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)–anchored protein,
whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly,
with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones
from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of …
myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has
been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)–anchored protein,
whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly,
with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones
from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of …
Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)–anchored protein, whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly, with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth. MAG-resistant embryonic neurons are rendered MAG-sensitive by expression of NgR. MAG and Nogo-66 activate NgR independently and serve as redundant NgR ligands that may limit axonal regeneration after CNS injury.