Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/7551
Título
Number and brightness analysis reveals that NCAM and FGF2 elicit different assembly and dynamics of FGFR1 in live cells
Autor(es)
Zamai, Moreno CNIC | Trullo, Antonio | Giordano, Marco | Corti, Valeria | Arza, Elvira CNIC | Francavilla, Chiara | Cavallaro, Ugo | Caiolfa, Valeria R CNIC
Fecha de publicación
2019-01-03
Cita
J Cell Sci. 2019; 132(1):jcs220624
Idioma
Inglés
Tipo de documento
journal article
Resumen
Both fibroblast growth factor-2 (FGF2) and neural cell adhesion molecule (NCAM) trigger FGF receptor 1 (FGFR1) signaling; however, they induce remarkably distinct receptor trafficking and cellular responses. The molecular basis of such a dichotomy and the role of distinct types of ligand-receptor interaction remain elusive. Number of molecules and brightness (N&B) analysis revealed that FGF2 and NCAM promote different FGFR1 assembly and dynamics at the plasma membrane. NCAM stimulation elicits long-lasting cycles of short-lived FGFR1 monomers and multimers, a behavior that might reflect a rapid FGFR1 internalization and recycling. FGF2, instead, induces stable dimerization at the dose that stimulates cell proliferation. Reducing the occupancy of FGFR1 in response to low FGF2 doses causes a switch towards cyclically exposed and unstable receptor dimers, consistently with previously reported biphasic response to FGF2 and with the divergent signaling elicited by different ligand concentrations. Similar instability was observed upon altering the endocytic pathway. Thus, FGF2 and NCAM induce differential FGFR1 clustering at the cell surface, which might account for the distinct intracellular fate of the receptor and, hence, for the different signaling cascades and cellular responses.
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