Our research focus is axon regeneration and the role of the proteins Reggie/Flotillin, Prion Protein (PrP), Thy-1 and Nogo.
Reggies are commonly known as microdomain/lipid raft proteins which communicate with the GPI-anchored proteins PrP and Thy-1 during axon growth. All are upregulated in fish retinal ganglion cells during retinal axon regeneration after lesion to the optic nerve. Downregulation of the Reggies blocks regeneration as well as neuronal differentiation in mammalian hippocampal neurons. In a collaboration with the University Hospital of Neurology (Prof. M. Bähr), Göttingen we aim at upregulating Reggies in rat retinal ganglion cells to promote axon regeneration in mammals.
The communication between Reggie and the GPI-anchored proteins promotes not only process formation in neurons but regulates important and basic events in many cell types, such as cell adhesion in epithelial and embryonic stem cells. The lab is currently characterizing the underlying signal transduction pathways in neurons as well as in standard cell types (HeLa and A431 cells). Results from our research indicate that the communication of PrP (and Thy-1) with Reggies leads to the recruitment of important trans-membrane receptors and adhesion molecules to distinct sites of the cell such as E-cadherin to cell-cell contact sites, the T cell receptor to the cap in T-lymphocytes and bulk membrane with growth receptors to growth cones of elongating axons. Several signal transducing proteins involved in the targeted delivery of cargo in dependence of PrP (Thy-1) and reggie have been identified and will be investigated in ongoing research in culture and in vivo in zebrafish.
Nogo-A/RTN-4-A in the environment of axons inhibits axon regeneration in mammals but fish RTN-4 does not interfere with axon growth. However, genome duplication has led to the emergence of RTN-6 in zebrafish. Our analysis suggests that RTN-6 in zebrafish is the Nogo-A homolog. Interestingly, zebrafish RTN-6 shows compelling similarities with neurocan in specific N-terminal domains. Current experiments examine how distinct RTN-6 domains affect axon growth, as well as when and where RTN-6 is expressed in the zebrafish nervous system to determine its function, effect on neurons and interaction with axonal receptors.