Characterization of glial cell line-derived neurotrophic factor family receptor alpha-1 in peripheral nerve Schwann cells.
Glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRalpha-1) is a receptor component of GDNF that associates with and activates the tyrosine kinase receptor Ret. To further understand GDNF and its receptor system in the PNS, we first characterized the expression of GFRalpha-1 in bovine peripheral nerve in vivo. GFRalpha-1 immunoreactivity was localized adjacent to the outermost layer of myelin sheath, as well as in the endoneurium and axoplasm. In a fractionation study, GFRalpha-1 was recovered mostly in the soluble fraction, although a small amount was recovered in the membrane fraction. A substantial amount of GFRalpha-1 in the membrane fraction was extractable by detergent and alkaline conditions. To further clarify the expression of GFRalpha-1 in Schwann cells, we examined cultured rat Schwann cells and the Schwannoma cell line RT4. Schwann cells expressed GFRalpha-1 in both the soluble/cytosolic and membrane fractions, and the membrane form of GFRalpha-1 was expressed at the outer surface of the Schwann cell plasma membrane. We also confirmed the secretion of the soluble form of GFRalpha-1 from Schwannoma cells in a metabolic labeling experiment. These data contribute to our knowledge of the production, expression and functions of GFRalpha-1 in the PNS.
Hase
Asako
A
Department of Neurology and Neuroscience, Teikyo University School of Medicine, Kaga, Tokyo Japan.
Saito
Fumiaki
F
Yamada
Hiroki
H
Arai
Ken
K
Shimizu
Teruo
T
Matsumura
Kiichiro
K
D000818:Animals; D001710:Biotin; D002417:Cattle; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D015151:Immunoblotting; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009442:Neurilemmoma / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism*
D003470:Culture Media; C495041:Gdnf protein, rat; C494989:Gfra1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D001710:Biotin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C495001:Ret protein, rat