A Novel Receptor for Myelin associated Glycoprotein

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DESCRIPTION (provided by applicant): The poor regenerative capacity of injured central nervous system (CNS) axons is largely due to growth inhibitory proteins associated with CNS myelin. Myelin-associated glycoprotein (MAG), a sialic acid binding lectin, inhibits neurite outgrowth in a neuraminidase sensitive manner. I have identified the Nogo Receptor (NgR1) homologue NgR2 as a novel and high affinity binding-partner for MAG. NgR2 supports MAG binding in a neuraminidase sensitive manner and ectopic expression of NgR2 is sufficient to confer MAG responsiveness upon neurons normally not inhibited by MAG. The experiments proposed are aimed at addressing whether NgR2 is necessary for MAG inhibition, determine the functional relationship between NgR1 and NgR2, and the NgR2 mechanism of action. I will use histochemical and biochemical procedures to ask whether NgR1 and NgR2 use conserved mechanisms to signal growth inhibition. NgR2 loss-of-function studies will be performed to examine whether NgR2 is necessary for MAG inhibition in primary neurons in vitro. It is anticipated that the studies proposed will further our understanding of the molecular mechanisms used by MAG to communicate growth inhibition to regenerating neurons.