A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor

  title={A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor},
  author={Robert D. Klein and Daniel Sherman and W H Ho and Donna M. Stone and Gregory L. Bennett and Barbara Moffat and Richard A. Vandlen and Laura Simmons and Qimin Gu and Joanne Hongo and Brigitte Devaux and Kris T. Poulsen and Mark P. Armanini and Chikateru Nozaki and Naoya Asai and Audrey San Francisco Goddard and Heidi Phillips and Christopher E. Henderson and Masahide Takahashi and Arnon Rosenthal},
Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent survival factors for sympathetic, sensory and central nervous system neurons. GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here… 
Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase
The cloning of a new GPI-linked receptor termed NTNR-α that is homologous with GDNFR-α and is widely expressed in the nervous system and other tissues is reported, indicating that GDNF and neurturin promote neuronal survival by signalling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI family of receptors that determines ligand specificity.
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-4 and the tyrosine kinase Ret form a functional receptor complex for persephin
Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions.
It is shown that the rate of dissociation of (125)I-GDNF from GFRalpha1 is increased in the presence of 50 nm GDNF, an effect that can be explained by the occurrence of negative cooperativity and the high affinity binding can be measured only when cRET is present.
Expression of neurturin, GDNF, and their receptors in the adult mouse CNS
The pattern of GF factor and receptor expression in the adult brain suggests a role for these factors in maintaining neuronal circuits in the mature CNS.
Expression of GDNF Family Receptor Components during Development: Implications in the Mechanisms of Interaction
There are multiple mechanisms regulating the interaction between Ret and the α-receptors that mediates the effects of GDNF family trophic factors on the survival and differentiation of cells and on neuron–target interactions in the nervous system.
Characterization of novel neutralizing monoclonal antibodies specific to human neurturin.
Novel, specific MAbs with varying epitope specificities and blocking activity will be valuable tools for both the in vitro and in vivo characterization of NTN and its relationship to the GFRalpha2 and Ret receptors.
The GDNF/Neurturin‐Ret multicomponent receptor system
Since GDNF and NTN are expected as therapeutic agents in neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis, the studies on the mechanisms of their biological actions through Ret would contribute to the development of new therapeutic strategies for these diseases.
Multiple GPI-Anchored Receptors Control GDNF-Dependent and Independent Activation of the c-Ret Receptor Tyrosine Kinase
Combined roles for GFR alpha receptors in the regulation of c-Ret activity and the maintenance of distinct neuronal circuits in the central and peripheral nervous systems are indicated.


Characterization of a multicomponent receptor for GDNF
It is demonstrated that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive cells and binds GDNF with a high affinity, which supports the hypothesis that GDNF uses a multi-subunit receptor system in which GDN FR-α and Ret function as the ligand-binding and signalling components.
Functional receptor for GDNF encoded by the c-ret proto-oncogene
It is shown that GDNF binds to, and induces tyrosine phosphorylation of, the product of the c-ret proto-oncogene, an orphan receptor tyrosin kinase, in a GDNF responsive motor-neuron cell line, which encodes a functional receptor for GDNF that may mediate its neurotrophic effects on motor and dopaminergic neurons.
GDNF signalling through the Ret receptor tyrosine kinase
It is shown that glial-cell-line-derived neurotrophic factor (GDNF)7, a distant member of the transforming growth factor(TGF)-β superfamily, signals through the Ret RTK, and that GDNF, in addition to its potential role in the differentiation and survival of central nervous system neurons8–12, has profound effects on kidney organogenesis and the development of the peripheral nervous system.
Neurturin, a relative of glial-cell-line-derived neurotrophic factor
THE normal development of the vertebrate nervous system entails the death of 30–70% of the neurons originally generated in most neuronal populations1. This naturally occurring cell death is regulated
Released form of CNTF receptor alpha component as a soluble mediator of CNTF responses.
These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functionalCNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand.
Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons
The findings indicate GDNF is a new neurotrophic factor for developing peripheral neurons and suggest possible non-neuronal roles for GDNF in the developing reproductive system.
GDNF in a Bind with Known Orphan: Accessory Implicated in New Twist
GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.
In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.