Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase

Anna Buj-Bello, Jimi Adu, Luzia G. P. Piñón, Antony Horton, Jane Thompson, Arnon Rosenthal, Miguel Chinchetru, Vladimir L. Buchman and Alun M. Davies ()
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Anna Buj-Bello: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Jimi Adu: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Luzia G. P. Piñón: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Antony Horton: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Jane Thompson: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Arnon Rosenthal: Genentech, Inc.
Miguel Chinchetru: Universidad de León
Vladimir L. Buchman: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews
Alun M. Davies: *School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews

Nature, 1997, vol. 387, issue 6634, 721-724

Abstract: Abstract Neurturin (NTN)1 is a recently identified homologue of glial-cell-line-derived neurotrophic factor (GDNF)2. Both factors promote the survival of a variety of neurons1,2,3,4,5, and GDNF is required for the development of the enteric nervous system and kidney6,7,8. GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor termed GDNFR-α9,10,11,12,13. Here we report 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. By using microinjection to introduce expression plasmids into neurons, we show that coexpression of NTNR-α with Ret confers a survival response to neurturin but not GDNF, and that coexpression of GDNFR-α with Ret confers a survival response to GDNF but not neurturin. Our findings indicate 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-linked family of receptors that determines ligand specificity.

Date: 1997
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DOI: 10.1038/42729

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