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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS049870-02
Application #
7060438
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Kleitman, Naomi
Project Start
2005-03-21
Project End
2007-12-20
Budget Start
2006-03-21
Budget End
2007-03-20
Support Year
2
Fiscal Year
2006
Total Cost
$44,085
Indirect Cost
Name
University of Rochester
Department
Neurology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627