The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking
- Francavilla, Chiara IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, I-20139 Milano, Italy
- Cattaneo, Paola IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, I-20139 Milano, Italy
- Berezin, Vladimir Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark
- Bock, Elisabeth Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark
- Ami, Diletta IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, I-20139 Milano, Italy
- de Marco, Ario IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, I-20139 Milano, Italy
- Christofori, Gerhard Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, CH-4058 Basel, Switzerland
- Cavallaro, Ugo IFOM-FIRC Institute of Molecular Oncology, IFOM-IEO Campus, I-20139 Milano, Italy
- 2009-12-28
Published in:
- Journal of Cell Biology. - Rockefeller University Press. - 2009, vol. 187, no. 7, p. 1101-1116
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1083/jcb.200903030
- ISSN 1540-8140
- Persistent URL
- https://sonar.rero.ch/global/documents/81450
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