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GDNF and Related Proteins

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Members of the glial‐cell‐line‐derived neurotrophic factor (GDNF) family serve important functions in development and maintenance of distinct sets of central and peripheral neurons. All four GDNF family ligands (GFLS), GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN), interact with a multi‐subunit receptor complex formed by the c‐Ret tyrosine kinase, Ret, and a cysteine‐rich glycosyl phosphatidylinositol‐anchored receptor (GDNF receptor alpha 1‐4). Since their discovery, GFLS have received particular attention because of their therapeutic potential in numerous neurological diseases, such as Parkinson's disease (PD), motor neuron diseases, or sensory regeneration and neuropathic pain. Targeted mutagenesis in transgenic mice has shown that Ret and GFL are required for multiple developmental events including the development of the enteric nervous system (ENS), which is affected in Hirschsprung's disease (HD). This chapter focuses on the molecular mechanisms of the initiation and the contextual dependence of signal transduction by GFL, their neuroprotective and neuroregenerative potential, and their involvement in developmental processes.

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Abbreviations

aa:

amino acid

ARTN:

artemin

CG:

ciliary ganglion

DRG:

dorsal root ganglion

ENS:

enteric nervous system

ERK:

extracellular signal‐regulated kinase

EST:

expressed sequence tag

FAK:

focal adhesion kinase

FMTC:

familial medullary thyroid carcinoma

GABA:

gamma‐aminobutyric acid

GDNF:

glial‐cell‐line‐derived neurotrophic factor

GFL:

GDNF family ligands

GFRα:

GDNF receptor alpha

GPI:

glycosyl phosphatidylinositol

HD:

Hirschsprung's disease

JNK:

Jun N‐terminal kinase

MAPK:

mitogen‐activated protein kinase

MEN2:

multiple endocrine neoplasia type 2

NCAM:

neuronal cell adhesion molecule

NGF:

nerve growth factor

NRTN:

neurturin

PC12:

pheochromocytoma cell line

PCR:

polymerase chain reaction

PD:

Parkinson's disease

PI3K:

phosphatidylinositol‐3 kinase

PLCγ:

phospholipase C gamma

PSPN:

persephin

Ret:

rearranged in transformation

Ret/PTC:

rearranged in transformation/papillary thyroid carcinomas

RTK:

receptor protein tyrosine kinase

SCG:

superior cervical ganglion

TGFβ:

transforming growth factor beta

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Acknowledgments

The authors’ work was supported by grants from the Deutsche Forschungsgemeinschaft (Str 616/3‐4) and from the MWK. We thank Dr. Katrin Huber for providing the in situ hybridization photographs and Prof. Dr. Dr. Klaus Unsicker for his suggestions regarding the manuscript.

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  1. H. Peterziel
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  2. J. Strelau
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurology (Division of Neurochemistry and Neurobiology), University of Iowa College of Medicine and Veterans Administration Medical Center, 52242, lowa, lowa, USA

    Ramon Lim

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Peterziel, H., Strelau, J. (2006). GDNF and Related Proteins. In: Lajtha, A., Lim, R. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30381-9_4

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