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

Nature
R D KleinA Rosenthal

Abstract

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-alpha) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha. We further demonstrate that NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity; that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN, in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These findings identify Ret and NTNR-alpha as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotro...Continue Reading

References

Apr 1, 1987·Molecular and Cellular Biology·M Takahashi, G M Cooper
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J PuginP S Tobias
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J D LeeR J Ulevitch
Aug 4, 1994·Nature·J L WranaJ Massagué
Jun 27, 1996·Nature·P DurbecM Saarma
Jul 4, 1996·Nature·M W MooreA Rosenthal
Jul 4, 1996·Nature·J J TreanorA Rosenthal
Oct 1, 1996·Neuron·R M Lindsay, G D Yancopoulos

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Citations

Aug 14, 1998·The Journal of Comparative Neurology·J P GoldenE M Johnson
Jun 26, 1999·Microscopy Research and Technique·M Saarma, H Sariola
Feb 12, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·K LuukkoI Thesleff
Oct 24, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·K LuukkoI Thesleff
May 14, 1999·Developmental Genetics·G R Dressler
May 14, 1999·Developmental Genetics·J A DaviesJ Milbrandt
Mar 10, 2001·Developmental Dynamics : an Official Publication of the American Association of Anatomists·A GarcèsO Delapeyrière
Jun 20, 2000·Diseases of the Colon and Rectum·C H KnowlesB A Ponder
Oct 13, 2006·Pituitary·Yoshiki MurakumoMasahide Takahashi
Oct 24, 1998·Trends in Neurosciences·C F Ibáñez
Jul 11, 2001·Endocrinology and Metabolism Clinics of North America·E Puxeddu, J A Fagin
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mehdi GasmiRaymond T Bartus
Jun 26, 2001·The European Journal of Neuroscience·O E OrozcoM Sanicola
Jan 5, 2011·The Journal of Biological Chemistry·Uwe JerkeRalph Kettritz
Dec 20, 2002·Thyroid : Official Journal of the American Thyroid Association·Salud BorregoGuillermo Antiñolo
Jan 26, 2007·Molecular Biology of the Cell·Xueyi LiJ Bernd Helms
Apr 16, 1998·Journal of the National Cancer Institute·D M DawsonT G Pretlow
Jul 20, 2006·International Anesthesiology Clinics·Elizabeth Vernon PittsRita J Balice-Gordon
Dec 22, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H KitagawaK Abe
Apr 26, 2006·Pathology International·Naoya AsaiMasahide Takahashi
Aug 3, 2012·Science Signaling·Amisha PatelHenrique Veiga-Fernandes
Jun 9, 2000·Annual Review of Physiology·A O HoffR F Gagel
Mar 10, 2001·Reviews in the Neurosciences·K M Giehl
Aug 30, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cynthia C Tsui, Brian A Pierchala
Jun 21, 2005·Genetics·Renee D ReadRoss L Cagan
Apr 6, 2005·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Yossef S LevyDaniel Offen
Apr 16, 1998·Biochemical and Biophysical Research Communications·S NomotoK Kiuchi
Dec 30, 1999·Journal of Endocrinological Investigation·M SantoroA Fusco

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