title: PGF2alpha increases FGF-2 and FGFR2 trafficking in Py1a rat osteoblasts via clathrin independent and importin beta dependent pathway.
abstract: Previous studies showed that prostaglandin F2alpha (PGF2alpha) stimulated fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 2 (FGFR2) cytosolic and nuclear accumulation, however, the endocytic pathway has not been elucidated. This study demonstrates that although PGF2alpha increased the formation of clathrin-coated structures in Py1a rat osteoblasts, they were not involved in FGF-2 and FGFR2 trafficking. PGF2alpha increased binding of FGF-2 and FGFR2 and co-localization of reactive sites in addition to nuclear translocation at the nuclear pore complex level. FGF-2 and FGFR2 were in close spatial correlation with importin beta, further supporting nuclear import of the FGF-2/FGFR2 complex. Immunogold and immunofluorescence techniques as well as Western blotting demonstrated increased importin beta protein labeling in response to PGF2alpha. Similar to PGF2alpha, phorbol 12-myristate 13-acetate (PMA) also increased importin beta protein. These data strongly suggest that prostaglandins may regulate osteoblast metabolism via FGF-2/FGFR2/importin beta nuclear trafficking.
authors.affiliation: Department of Comparative Morphology and Biochemistry, University of Camerino, Camerino (MC)/Italy. luigi.marchetti@unicam.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Marchetti
authors.forename: Maria G
authors.initials: MG
authors.lastname: Sabbieti
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Agas
authors.forename: Maura
authors.initials: M
authors.lastname: Menghi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Materazzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Menghi
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D051381:Rats; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D015398:Signal Transduction; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D002966:Clathrin; D028961:beta Karyopherins; D016222:Fibroblast Growth Factor 2; D015237:Dinoprost; D051497:Receptor, Fibroblast Growth Factor, Type 2