Project Details
Projekt
Role of Nogo-B and its novel cognate receptor in the cardiovascular system
Applicant
Dr. Michael Schleicher
Subject Area
Anatomy and Physiology
Term
from 2005 to 2007
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 20066835
The Nogo isoforms -A, -B, and -C are transmembrane proteins which belong to the reticulon family. While Nogo-A is expressed in the central nervous system and serves as an endogenous inhibitor of axonal growth and repair, little is known about the function or significance of the other Nogo isoforms. Recent data show that Nogo-B is highly enriched in caveolae of endothelial and smooth muscle cells as well as in intact blood vessels. Nogo-B promotes migration of endothelial cells while antagonizing the migration of vascular smooth muscle cells. Unlike Nogo-A, Nogo-B thereby acts via its amino terminus. Disruption of the Nogo-A/B gene impairs the response to vascular injury and tissue ischemia resulting in an exaggerated neointimal proliferation and diminished ischemic reserve capacity. Gene transfer of Nogo-B rescues these phenotypes. In addition, a novel receptor for the amino terminus of Nogo-B has been cloned which is highly expressed in vascular cells. Thus, the hypothesis arises that Nogo-B binding to its cognate receptor is a novel regulatory system coordinating vascular response to injury or tissue ischemia. Therefore the following research objectives are proposed: 1. Definition of the role of Nogo-B during arteriogenesis and angiogenesis; 2. Characterization of the receptor for Nogo-B in vascular cells and the physiological consequences upon ligand binding. These experiments will help to define the role of Nogo-B in the vasculature and may lead to potential therapies modulating angiogenesis, arteriogenesis and vascular remodeling.
DFG Programme
Research Fellowships
International Connection
USA
