F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion

H. Peterziel*, T. Sackmann, J. Strelau, P. H. Kuhn, S. F. Lichtenthaler, K. Marom, A. Klar, K. Unsicker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageAmerican English
Pages (from-to)483-497
Number of pages15
JournalMolecular and Cellular Neuroscience
Volume46
Issue number2
DOIs
StatePublished - Feb 2011

Bibliographical note

Funding Information:
We thank Jutta Fey, Martina Scharpff, Ulla Hinz, Gerald Bendner and Ingeborg Vogt for excellent technical assistance. The GST-RAP construct was kindly provided by J. Herz (Department of Molecular Genetics, University of Texas Southwestern, Dallas, Texas). This work was supported by a grant from the German–Israel Foundation (GIF) to A.K. and K.U. and by the DFG through SFB596 to S.F.L. and through SFB 592 to K.U.

Keywords

  • APP
  • Ciliary ganglion
  • Disabled-1
  • Extracellular matrix
  • F-spondin
  • Programmed cell death
  • Transforming growth factor-beta

Fingerprint

Dive into the research topics of 'F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion'. Together they form a unique fingerprint.

Cite this