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

doi:10.1016/j.mcn.2010.12.001

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

Department of Medical Neurobiology

Research output: Contribution to journal › Article › peer-review

10 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 language	American English
Pages (from-to)	483-497
Number of pages	15
Journal	Molecular and Cellular Neurosciences
Volume	46
Issue number	2
DOIs	https://doi.org/10.1016/j.mcn.2010.12.001
State	Published - 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

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10.1016/j.mcn.2010.12.001

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@article{10410d71d00149609cd107ea8a02dbd6,

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

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.",

keywords = "APP, Ciliary ganglion, Disabled-1, Extracellular matrix, F-spondin, Programmed cell death, Transforming growth factor-beta",

author = "H. Peterziel and T. Sackmann and J. Strelau and Kuhn, {P. H.} and Lichtenthaler, {S. F.} and K. Marom and A. Klar and K. Unsicker",

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.",

year = "2011",

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doi = "10.1016/j.mcn.2010.12.001",

language = "American English",

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journal = "Molecular and Cellular Neurosciences",

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AU - Peterziel, H.

AU - Sackmann, T.

AU - Strelau, J.

AU - Kuhn, P. H.

AU - Lichtenthaler, S. F.

AU - Marom, K.

AU - Klar, A.

AU - Unsicker, K.

N1 - 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.

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

KW - APP

KW - Ciliary ganglion

KW - Disabled-1

KW - Extracellular matrix

KW - F-spondin

KW - Programmed cell death

KW - Transforming growth factor-beta

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U2 - 10.1016/j.mcn.2010.12.001

DO - 10.1016/j.mcn.2010.12.001

M3 - Article

AN - SCOPUS:78751704969

SN - 1044-7431

VL - 46

SP - 483

EP - 497

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

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