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Institute for Regenerative Medicine • IREM

Research Interests

Signalling mechanisms of neurite outgrowth

20 years ago we discovered the nerve fiber growth inhibiting protein Nogo-A. We described that Nogo-A is mainly present in the myelin sheath surrounding axons and we developed functionally blocking antibodies against Nogo-A to confirm its inhibitory role in cell culture experiments and in vivo.

The Nogo receptor complex and Nogo induced intracellular signaling

An Nogo-A fragment analysis has demonstrated the existence of 2 active sites for inhibition of neurite outgrowth. The Nogo-A-specific delta-20 active site binds with high affinity to the G-protein coupled receptor S1PR2 and activates G13 signalling to the small GTPase RhoA. The Nogo-66 sequence is known to bind to the Nogo receptor NgR-1 which also activates RhoA. RhoA and ROCK inactivate the membrane associated actin cytoskeleton, thereby leading to collapse of growth cones and growth arrest. Nogo-A and its receptors can be internalized and transported from axon terminals to the neuronal cell body as signalling endosomes. In the cell body, growth suppression occurs via downregulation of neuronal growth pathways.