GFRα3 is an orphan member of the GDNF/neurturin/persephin receptor family

GFRα3 is an orphan member of the GDNF/neurturin/persephin receptor family

Departments of ^*Pathology and Internal Medicine and ^†Neurology, Molecular Biology, and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110; and ^‡Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255

Communicated by Stanley J. Korsmeyer, Washington University School of Medicine, St. Louis, MO (received for review February 4, 1998)

Abstract

GDNF, neurturin, and persephin are transforming growth factor β-related neurotrophic factors known collectively as the GDNF family (GF). GDNF and neurturin signal through a multicomponent receptor complex containing a signaling component (the Ret receptor tyrosine kinase) and either of two glycosyl-phosphatidylinositol-linked binding components (GDNF family receptor α components 1 and 2, GFRα1 or GFRα2), whereas the receptor for persephin is unknown. Herein we describe a third member of the GF coreceptor family called GFRα3 that is encoded by a gene located on human chromosome 5q31.2–32. GFRα3 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. GFRα3 is also expressed at high levels in developing, but not adult, peripheral nerve. GFRα3 is a glycoprotein that is glycosyl-phosphatidylinositol-linked to the cell surface like GFRα1 and GFRα2. Fibroblasts expressing Ret and GFRα3 do not respond to any of the known members of the GDNF family, suggesting that GFRα3 interacts with an unknown ligand or requires a different or additional signaling protein to function.

Footnotes

↵ § To whom reprint requests should be addressed. e-mail: jeff{at}milbrandt.wustl.edu.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF051766 for mouse GFRα3 and AF051767 for human GFRα3).
ABBREVIATIONS:

GDNF,

glial cell line-derived neurotrophic factor;

NTN,

neurturin: PSP, persephin;

GF,

GDNF family;

GFRα,

GDNF family receptor α component;

GPI,

glycosyl-phosphatidylinositol;

CNS,

central nervous system;

PNS,

peripheral nervous system;

DRG,

dorsal root ganglion;

EST,

expressed sequence tag;

HA,

hemagglutinin;

MRB,

master RNA blot;

E,

embryonic day(s)