Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF

Janne Nielsen; Kamil Gotfryd; Shizhong Li; Nikolaj Kulahin; Vladislav Soroka; Kim K Rasmussen; Elisabeth Bock; Vladimir Berezin

doi:10.1523/JNEUROSCI.3239-09.2009

Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF

Janne Nielsen, Kamil Gotfryd, Shizhong Li, Nikolaj Kulahin, Vladislav Soroka, Kim K Rasmussen, Elisabeth Bock, Vladimir Berezin

60 Citations (Scopus)

Abstract

The formation of appropriate neuronal circuits is an essential part of nervous system development and relies heavily on the outgrowth of axons and dendrites and their guidance to their respective targets. This process is governed by a large array of molecules, including glial cell line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM), the interaction of which induce neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF-induced neurite outgrowth were investigated in cultures of hippocampal neurons, which do not express Ret. We demonstrate that NCAM-mediated GDNF-induced signaling leading to neurite outgrowth is more complex than previously reported. It not only involves NCAM-140 and the Src family kinase Fyn but also uses NCAM-180 and the fibroblast growth factor receptor. We find that induction of neurite outgrowth by GDNF via NCAM or by trans-homophilic NCAM interactions are not mutually exclusive. However, whereas NCAM-induced neurite outgrowth primarily is mediated by NCAM-180, we demonstrate that GDNF-induced neurite outgrowth involves both NCAM-140 and NCAM-180. We also find that GDNF-induced neurite outgrowth via NCAM differs from NCAM-induced neurite outgrowth by being independent of NCAM polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore, we identify within the heel region of GDNF a binding site for NCAM and demonstrate that a peptide encompassing this sequence mimics the effects of GDNF with regard to NCAM binding, activation of intracellular signaling, and induction of neurite outgrowth.

Original language	English
Journal	Journal of Neuroscience
Volume	29
Issue number	36
Pages (from-to)	11360-76
Number of pages	16
ISSN	0270-6474
DOIs	https://doi.org/10.1523/JNEUROSCI.3239-09.2009
Publication status	Published - 2009

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Nielsen, J., Gotfryd, K., Li, S., Kulahin, N., Soroka, V., Rasmussen, K. K., Bock, E., & Berezin, V. (2009). Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. Journal of Neuroscience, 29(36), 11360-76. https://doi.org/10.1523/JNEUROSCI.3239-09.2009

Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF. / Nielsen, Janne; Gotfryd, Kamil; Li, Shizhong et al.

In: Journal of Neuroscience, Vol. 29, No. 36, 2009, p. 11360-76.

Research output: Contribution to journal › Journal article › Research › peer-review

Nielsen, J, Gotfryd, K, Li, S, Kulahin, N, Soroka, V, Rasmussen, KK, Bock, E & Berezin, V 2009, 'Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF', Journal of Neuroscience, vol. 29, no. 36, pp. 11360-76. https://doi.org/10.1523/JNEUROSCI.3239-09.2009

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title = "Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF",

abstract = "The formation of appropriate neuronal circuits is an essential part of nervous system development and relies heavily on the outgrowth of axons and dendrites and their guidance to their respective targets. This process is governed by a large array of molecules, including glial cell line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM), the interaction of which induce neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF-induced neurite outgrowth were investigated in cultures of hippocampal neurons, which do not express Ret. We demonstrate that NCAM-mediated GDNF-induced signaling leading to neurite outgrowth is more complex than previously reported. It not only involves NCAM-140 and the Src family kinase Fyn but also uses NCAM-180 and the fibroblast growth factor receptor. We find that induction of neurite outgrowth by GDNF via NCAM or by trans-homophilic NCAM interactions are not mutually exclusive. However, whereas NCAM-induced neurite outgrowth primarily is mediated by NCAM-180, we demonstrate that GDNF-induced neurite outgrowth involves both NCAM-140 and NCAM-180. We also find that GDNF-induced neurite outgrowth via NCAM differs from NCAM-induced neurite outgrowth by being independent of NCAM polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore, we identify within the heel region of GDNF a binding site for NCAM and demonstrate that a peptide encompassing this sequence mimics the effects of GDNF with regard to NCAM binding, activation of intracellular signaling, and induction of neurite outgrowth.",

author = "Janne Nielsen and Kamil Gotfryd and Shizhong Li and Nikolaj Kulahin and Vladislav Soroka and Rasmussen, {Kim K} and Elisabeth Bock and Vladimir Berezin",

note = "Keywords: Amino Acid Sequence; Animals; Binding Sites; Cell Line; Cells, Cultured; Glial Cell Line-Derived Neurotrophic Factor; Humans; Molecular Sequence Data; Neural Cell Adhesion Molecules; Neurites; Rats; Rats, Wistar",

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T1 - Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF

AU - Nielsen, Janne

AU - Gotfryd, Kamil

AU - Li, Shizhong

AU - Kulahin, Nikolaj

AU - Soroka, Vladislav

AU - Rasmussen, Kim K

AU - Bock, Elisabeth

AU - Berezin, Vladimir

N1 - Keywords: Amino Acid Sequence; Animals; Binding Sites; Cell Line; Cells, Cultured; Glial Cell Line-Derived Neurotrophic Factor; Humans; Molecular Sequence Data; Neural Cell Adhesion Molecules; Neurites; Rats; Rats, Wistar

PY - 2009

Y1 - 2009

N2 - The formation of appropriate neuronal circuits is an essential part of nervous system development and relies heavily on the outgrowth of axons and dendrites and their guidance to their respective targets. This process is governed by a large array of molecules, including glial cell line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM), the interaction of which induce neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF-induced neurite outgrowth were investigated in cultures of hippocampal neurons, which do not express Ret. We demonstrate that NCAM-mediated GDNF-induced signaling leading to neurite outgrowth is more complex than previously reported. It not only involves NCAM-140 and the Src family kinase Fyn but also uses NCAM-180 and the fibroblast growth factor receptor. We find that induction of neurite outgrowth by GDNF via NCAM or by trans-homophilic NCAM interactions are not mutually exclusive. However, whereas NCAM-induced neurite outgrowth primarily is mediated by NCAM-180, we demonstrate that GDNF-induced neurite outgrowth involves both NCAM-140 and NCAM-180. We also find that GDNF-induced neurite outgrowth via NCAM differs from NCAM-induced neurite outgrowth by being independent of NCAM polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore, we identify within the heel region of GDNF a binding site for NCAM and demonstrate that a peptide encompassing this sequence mimics the effects of GDNF with regard to NCAM binding, activation of intracellular signaling, and induction of neurite outgrowth.

AB - The formation of appropriate neuronal circuits is an essential part of nervous system development and relies heavily on the outgrowth of axons and dendrites and their guidance to their respective targets. This process is governed by a large array of molecules, including glial cell line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM), the interaction of which induce neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF-induced neurite outgrowth were investigated in cultures of hippocampal neurons, which do not express Ret. We demonstrate that NCAM-mediated GDNF-induced signaling leading to neurite outgrowth is more complex than previously reported. It not only involves NCAM-140 and the Src family kinase Fyn but also uses NCAM-180 and the fibroblast growth factor receptor. We find that induction of neurite outgrowth by GDNF via NCAM or by trans-homophilic NCAM interactions are not mutually exclusive. However, whereas NCAM-induced neurite outgrowth primarily is mediated by NCAM-180, we demonstrate that GDNF-induced neurite outgrowth involves both NCAM-140 and NCAM-180. We also find that GDNF-induced neurite outgrowth via NCAM differs from NCAM-induced neurite outgrowth by being independent of NCAM polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore, we identify within the heel region of GDNF a binding site for NCAM and demonstrate that a peptide encompassing this sequence mimics the effects of GDNF with regard to NCAM binding, activation of intracellular signaling, and induction of neurite outgrowth.

U2 - 10.1523/JNEUROSCI.3239-09.2009

DO - 10.1523/JNEUROSCI.3239-09.2009

M3 - Journal article

C2 - 19741142

SN - 0270-6474

VL - 29

SP - 11360

EP - 11376

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

IS - 36

ER -