The signaling mechanisms and normal functions of the Nogo receptor will be investigated. Recent evidence indicates that the Nogo receptor (NogoR) signals by forming a complex with the p75 neurotrophin receptor (p75NTR). Uncharacterized structural homologs of both NogoR and p75NTR exist. It will be determined whether these homologs also form complexes and whether they signal similarly to the NogoR/p75NTR complex, via Nogo or MAG-dependent activation of RhoA and NF-kappaB. These studies will involve molecular cloning of mouse and zebrafish NogoR homologs, and expression in cultured mammalian cell lines of transfected NogoR, NogoR homolog, p75NTR and p75NTR homologs. Previous studies indicate that NogoR/p75NTR signaling functions to inhibit regeneration of the injured adult spinal cord. It is postulated that NogoR/p75NTR and homologs also function during embryonic development to guide neural axons to their appropriate targets. This hypothesis will be tested by employing morpholino-antisense RNA technology to disrupt expression of these proteins in zebrafish embryos. Effects of these manipulations on axonal targeting will be assessed by injecting the fluorescent marker Dil into embryos to allow microscopic imaging of axon trajectories.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS047348-03
Application #
6998453
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Mamounas, Laura
Project Start
2004-01-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
3
Fiscal Year
2006
Total Cost
$338,841
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Meabon, James S; De Laat, Rian; Ieguchi, Katsuaki et al. (2015) LINGO-1 protein interacts with the p75 neurotrophin receptor in intracellular membrane compartments. J Biol Chem 290:9511-20
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