GDNF Family Neurotrophic Factor Signaling: Four Masters, One Servant?

  title={GDNF Family Neurotrophic Factor Signaling: Four Masters, One Servant?},
  author={Matti S. Airaksinen and Alexey Titievsky and Mart Saarma},
  journal={Molecular and Cellular Neuroscience},
It is concluded that sympathetic progenitors are a hybrid population expressing markers of both the cholinergic and noradrenergic lineage and that the homeobox transcription factor HMX1 is required both for the repression of the expression of Ret and other cholinergic markers and for the maintenance of nor adrenergic marker expression.
Molecular and Cellular Characterization of Dopamine Neuron Stimulating Peptides
Three peptides are characterized to determine it they are stable and offer protective effects similar to GNDF allowing them to be potential therapeutic molecules, and the interaction between DNSP-11 and GAPDH was evaluated as a potential anti-apoptotic mechanism.
Actions of GDNF on Midbrain Dopaminergic Neurons: The Signaling Pathway
The present review focuses on the correlates of neurotrophic factors and PD treatments, and the mechanisms of action of GDNF.
Comparison of GFL-GFRalpha complexes: further evidence relating GFL bend angle to RET signalling.
  • V. Parkash, A. Goldman
  • Chemistry
    Acta crystallographica. Section F, Structural biology and crystallization communications
  • 2009
By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling.
Rewiring ret : PTB-adaptor regulated signaling and cell biology
Ret has been rewired to preferentially bind one PTB-adaptor on the expense of others to tyrosine 1062, which makes it possible to experimentally assign biochemical events as well as cell biological outcomes to one specific adaptor and so increasingly reveal how one common receptor may serve a plethora of functions depending on the subcellular milieu in which it operates.
Altered expression of neurotrophic factors in patients with major depression.
GDNF Family Ligands Trigger Indirect Neuroprotective Signaling in Retinal Glial Cells
A detailed model of GDNF-induced signaling in mammalian retina is provided and it is proposed that the GDNF -induced rescue effect on mutated photoreceptors is an indirect effect mediated by retinal Mueller glial cells.
A model for GFRα4 function and a potential modifying role in multiple endocrine neoplasia 2
The data suggest a model of wild-type GFRα4 isoform expression that includes both activating and inhibiting co-receptors for RET, and a candidate for glial cell line-derived neurotrophic factor receptor alpha 4 (GFRA4), which encodes a cell surface-bound co- receptor required for interaction of RET with its ligand persephin.


GFRα3 is an orphan member of the GDNF/neurturin/persephin receptor family
A third member of the GF coreceptor family called GFRα3 that is encoded by a gene located on human chromosome 5q31.2–32 is described, which is not expressed in the central nervous system of the developing or adult animal but is highly expressed in several developing and adult sensory and sympathetic ganglia of the peripheral nervous system.
Molecular Cloning and Expression Analysis of GFRα-3, a Novel cDNA Related to GDNFRα and NTNRα
Results indicate that the tissue distribution of GFR alpha-3 mRNA is different from that of GDNFR alpha or NTNR alpha mRNA, and suggest that GFRalpha-3 may function in differentiation of embryonic cells expressing its mRNA.
GFRα-2 and GFRα-3 Are Two New Receptors for Ligands of the GDNF Family
The receptor for glial cell line-derived neurotrophic factor (GDNF) consists of GFRα-1 and Ret, and it is reported that neurturin can bind to either GFR α-1 or G FRα-2, a novel receptor related to GFRβ, suggesting that GFRs mediate the action of GDNF family ligands in vivo.
GFRα-4, a New GDNF Family Receptor
The findings extend the family of GFRα proteins and provide information about the tissues in which GFR α-4 may function during development and predict a 431-amino-acid secreted protein that is more closely related to G FRα-1 and GFRalpha-2 than to GFRβ-3.
The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma
It is demonstrated that Tyr-539 of Ret/ptc2 (Tyr-761 on the proto-RET product) is an essential docking site for the full transforming potential of the oncogene, and PLCgamma is identified as a downstream effector ofRet/ptcs and suggested that this transducing molecule could play a crucial role in neoplastic signalling triggered by Ret/PTc oncoproteins.
Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons.
It is demonstrated that NTN induces Ret phosphorylation in primary cultures of rat superior cervical ganglion (SCG) neurons, and data indicate that NTn is a physiologically relevant ligand for the Ret receptor and suggest thatNTN may have a critical role in the development of many neuronal populations.
Mutations of the RET-GDNF signaling pathway in Ondine's curse.
This study was supported by the Association pour la Recherche sur le Cancer, the Association Francaise contre les Myopathies, and the Projet Hospitalier de Recherche Clinique (grant AOA94060). We
Glial Cell Line-derived Neurotrophic Factor Signals through the RET Receptor and Activates Mitogen-activated Protein Kinase*
It is demonstrated that GDNF treatment of several neuroblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-β family members are not able to activate the RET receptors.