OMgp LRR181-228: The Predominant Domain of OMgp in Neurite Outgrowth Inhibition

Abstract

Several observations suggest that the leucine-rich repeats (LRR) domain of oligodendrocyte-myelin glycoprotein (OMgp) may play an important role in inhibition of neurite outgrowth and axonal regeneration after brain injury. To better understand structure-function relationships for the OMgp LRR domain and its effects in neurite regeneration, distinct OMgp leucine-rich repeat were deleted by PCR based site-directed mutagenesis. The gene deleted OMgp LRR fragments were expressed with GST protein and the expressed proteins were used to culture with NgR-expressing CHO and hippocampal neurons. Results show that the deletion of OMgp amino acid residues 25-56, 57-133,134-180 did not interrupt its effects in binding NgR-expressing CHO and inhibiting hippocampal neurons growth. But the fragment deleted amino acid residues 181-228 can only bind with NgR-expressing CHO and lost the effect of neurite outgrowth inhibition. Results suggest that the OMgp amino acid 181-228 is the predominant domain in neurite outgrowth inhibition of OMgp. The OMgp LRR fragment without amino acid residues 181-228 may be a potent reagent for encouraging regeneration in the adult central nervous system following injury.