The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking.
Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor (FGF) receptor-1 (FGFR1). However, the biological significance of this interaction remains largely elusive. In this study, we show that NCAM induces a specific, FGFR1-mediated cellular response that is remarkably different from that elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1, NCAM promotes the stabilization of the receptor, which is recycled to the cell surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is required for NCAM-induced sustained activation of various effectors. Furthermore, NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1 recycling and sustained Src activation. Our results implicate NCAM as a nonconventional ligand for FGFR1 that exerts a peculiar control on the intracellular trafficking of the receptor, resulting in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor activation.
Francavilla
Chiara
C
IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, Milano, Italy.
Cattaneo
Paola
P
Berezin
Vladimir
V
Bock
Elisabeth
E
Ami
Diletta
D
de Marco
Ario
A
Christofori
Gerhard
G
Cavallaro
Ugo
U
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D015398:Signal Transduction
D008024:Ligands; D019006:Neural Cell Adhesion Molecules; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1