1. F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion
- Author
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Peterziel, H., Sackmann, T., Strelau, J., Kuhn, P.H., Lichtenthaler, S.F., Marom, K., Klar, A., and Unsicker, K.
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CILIARY ganglion , *TRANSFORMING growth factors-beta , *EXTRACELLULAR matrix , *CELL death , *THROMBOSPONDINS , *IMMUNOGLOBULINS , *GENE expression - Abstract
Abstract: The extracellular membrane-associated protein F-spondin has been implicated in cell–matrix and cell–cell adhesion and plays an important role in axonal pathfinding. We report here that F-spondin is expressed in non-neuronal cells in the embryonic chicken ciliary ganglion (CG) and robustly promotes survival of cultured CG neurons. Using deletion constructs of F-spondin we found that the amino-terminal Reelin/Spondin domain cooperates with thrombospondin type 1 repeat (TSR) 6, a functional TGFβ-activation domain. In ovo treatment with blocking antibodies raised against the Reelin/Spondin domain or the TSR-domains caused increased apoptosis of CG neurons during the phase of programmed cell death and loss of about 30% of the neurons compared to controls. The Reelin/Spondin domain receptor — APP and its downstream signalling molecule disabled-1 are expressed in CG neurons. F-spondin induced rapid phosphorylation of disabled-1. Moreover, both blocking the central APP domain and interference with disabled-1 signalling disrupted the survival promoting effect of F-spondin. Taken together, our data suggest that F-spondin can promote neuron survival by a mechanism involving the Reelin/Spondin and the TSR domains. [Copyright &y& Elsevier] more...
- Published
- 2011
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