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oai:repisalud.isciii.es:20.500.12105/75512024-09-27T10:08:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19607

00925njm 22002777a 4500 dc Zamai, Moreno author Trullo, Antonio author Giordano, Marco author Corti, Valeria author Arza, Elvira author Francavilla, Chiara author Cavallaro, Ugo author Caiolfa, Valeria R author 2019-01-03 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. J Cell Sci. 2019; 132(1):jcs220624 10.1242/jcs.220624 1477-9137 0021-9533 Journal of cell science 30478195 http://hdl.handle.net/20.500.12105/7551 FGF FGFR1 FGFR1 clustering FGFR1 signaling N&B analysis NCAM Receptor clustering Number and brightness analysis reveals that NCAM and FGF2 elicit different assembly and dynamics of FGFR1 in live cells