title: Retention in the Golgi apparatus and expression on the cell surface of Cfr/Esl-1/Glg-1/MG-160 are regulated by two distinct mechanisms.
abstract: Cfr (cysteine-rich fibroblast growth factor receptor) is an Fgf (fibroblast growth factor)-binding protein without a tyrosine kinase. We have shown previously that Cfr is involved in Fgf18 signalling via Fgf receptor 3c. However, as Cfr is also known as Glg (Golgi apparatus protein)-1 or MG-160 and occurs in the Golgi apparatus, it remains unknown how the distribution of Cfr is regulated. In the present study, we performed a mutagenic analysis of Cfr to show that two distinct regions contribute to its distribution and stability. First, the C-terminal region retains Cfr in the Golgi apparatus. Secondly, the Cfr repeats in the extracellular juxtamembrane region destabilizes Cfr passed through the Golgi apparatus. This destabilization does not depend on the cleavage and secretion of the extracellular domain of Cfr. Furthermore, we found that Cfr with a GPI (glycosylphosphatidylinositol) anchor was predominantly expressed on the cell surface in Ba/F3 cells and affected Fgf18 signalling in a similar manner to the full-length Cfr, indicating that the interaction of Cfr with Fgfs on the cell surface is important for its function in Fgf signalling. These results suggest that the expression of Cfr in the Golgi apparatus and on the plasma membrane is finely tuned through two distinct mechanisms for exhibiting different functions.
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miyaoka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kato
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ebato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Naoko
authors.initials: N
authors.lastname: Miyata
authors.forename: Toru
authors.initials: T
authors.lastname: Imamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
mesh_terms: D000818:Animals; D018968:CD58 Antigens / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000502:physiology; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018968:CD58 Antigens; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors