Nomenclature of GPI-Linked Receptors for the GDNF Ligand Family

Abstract

Members of the glial cell line–derived neurotrophic factor (GDNF) family, including GDNF and neurturin (NTN), play key roles in the control of vertebrate neuron survival and differentiation. GDNF and NTN signal via a multicomponent receptor system formed by a glycosyl-phosphatidylinositol (GPI)-linked ligand binding subunit (the “α” component) and the receptor tyrosine kinase RET as a signaling (i. e. “β”) subunit. To date, two distinct genes encoding α receptor components for GDNF and NTN have been reported in the literature. The first member of this receptor family, GDNF receptor-α (GDNFR-α) was shown to bind GDNF and to mediate binding and activation of the RET receptor tyrosine kinase (3Jing S.Q. Wen D.Z. Yu Y.B. Holst P.L. Luo Y. Fang M. Tamir R. Antonio L. Hu Z. Cupples R. Louis J.C. Hu S. Altrock B.W. Fox G.M. Cell. 1996; 85: 1113-1124Abstract Full Text Full Text PDF PubMed Scopus (1016) Google Scholar, 7Treanor J. Goodman L. Desauvage F. Stone D.M. Poulsen K.T. Beck C.D. Gray C. Armanini M.P. Pollock R.A. Hefti F. Phillips H.S. Goddard A. Moore M.W. Bujbello A. Davies A.M. Asai N. Takahashi M. Vandlen R. Henderson C.E. Rosenthal A. Nature. 1996; 382: 80-83Crossref PubMed Scopus (943) Google Scholar). The second member has been shown to bind NTN and to mediate activation of RET by both NTN and GDNF (1Baloh R.H. Tansey M.G. Golden J.P. Creedon D.J. Heuckeroth R.O. Keck C.L. Zimonjic D.B. Popescu N.C. Johnson E.M. Milbrandt J. Neuron. 1997; 18: 793-802Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 2Bujbello A. Adu J. Pinon L. Horton A. Thompson J. Rosenthal A. Chinchetru M. Buchman V.L. Davies A.M. Nature. 1997; 387: 721-724Crossref PubMed Scopus (253) Google Scholar, 4Klein R.D. Sherman D. Ho W.H. Stone D. Bennett G.L. Moffat B. Vandlen R. Simmons L. Gu Q.M. Hongo J.A. Devaux B. Poulsen K. Armanini M. Nozaki C. Asai N. Goddard A. Phillips H. Henderson C.E. Takahashi M. Rosenthal A. Nature. 1997; 387: 717-721Crossref PubMed Scopus (340) Google Scholar, 5Sanicola M. Hession C. Worley D. Carmillo P. Ehrenfels C. Walus L. Robinson S. Jaworski G. Wei H. Tizard R. Whitty A. Pepinsky R.B. Cate R.L. Proc. Natl. Acad. Sci. USA. 1997; 94: 6238-6243Crossref PubMed Scopus (272) Google Scholar, 6Suvanto P. Wartiovaara K. Lindahl M. Arumäe U. Moshnyakov M. Horelli-Kuitunen N. Airaksinen M.S. Palotie A. Sariola H. Saarma M. Hum. Mol. Gen. 1997; 6: 1267-1273Crossref PubMed Scopus (81) Google Scholar). This protein has been alternatively named TrnR-2, NTNR-α, RETL2, and GDNFR-β. Additional members of the GDNF ligand family as well as α receptor components are known to exist. In an effort to arrive at a sensible and easy to use consensus nomenclature for the α receptor components for the GDNF ligand family, several of us who have been involved in the identification and characterization of these receptors have formed a committee with the objective of proposing a nomenclature for the members of this receptor family. We propose to use the abbreviated name “GFRα-X” (for “GDNF Family Receptor Alpha-X”) where “X” denotes an arabic numeral to be assigned based on the date of publication of the receptor. Thus, GDNFR-α will become GFRα-1, while NTNR-α/TrnR-2/RETL2/GDNFR-β will be GFRα-2. The root name for the corresponding gene will be GFRα-X. We feel that this nomenclature is flexible enough to allow for the possibility of cross-talk between ligands and receptors. In addition, the use of the term “alpha” will serve to clarify the fact that these molecules are part of a multicomponent receptor complex and are all structurally related. We strongly encourage all investigators of GDNF family ligands and receptors to adopt these nomenclature recommendations in order to achieve our goal of improving communication between researchers both inside and outside this exciting field.1The following scientists have endorsed this nomenclature: Alun M. Davies, Jack E. Dixon, Gary M. Fox, Carlos F. Ibáñez* (chair), Shuqian Jing, Eugene Johnson, Jeffrey Milbrandt, Heidi Phillips, Arnon Rosenthal, Mart Saarma, Michele Sanicola, James Treanor, and Quinn C. Vega. *Laboratory of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden ([email protected])*Laboratory of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden ([email protected])