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CAM-FGF Receptor Interactions: A Model for Axonal Growth
1Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, London, SE1 9RT, United Kingdom
Molecular and Cellular Neurosciences
|August 1, 1996
Summary
Neural cell adhesion molecules (NCAMs) like N-cadherin and L1 stimulate axonal growth by activating the fibroblast growth factor receptor (FGFR) pathway, leading to neurite outgrowth.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neural cell adhesion molecules (NCAMs), including N-cadherin and L1, are known to promote axonal growth.
- Previous research identified a tyrosine kinase-PLCgamma cascade crucial for neurite outgrowth stimulated by these CAMs.
- Integrins do not mediate this specific growth response.
Purpose of the Study:
- To propose that fibroblast growth factor receptor (FGFR) activation in neurons mediates CAM-stimulated neurite outgrowth.
- To elucidate the downstream signaling events involving PLCgamma, calcium influx, and arachidonic acid production.
- To investigate the potential direct interaction between CAMs and FGFR based on conserved binding motifs.
Main Methods:
- Review of existing experimental paradigms demonstrating CAM-stimulated axonal growth.
- Analysis of molecular agents inhibiting and activating the PLCgamma cascade.
- Examination of evolutionary conserved binding motifs between CAMs and FGFR.
Main Results:
- Neurite outgrowth stimulated by NCAM, N-cadherin, and L1 is proposed to be mediated by FGFR activation.
- FGFR activation leads to PLCgamma recruitment and activation via SH2 domain interactions.
- Downstream events include DAG conversion to arachidonic acid and increased neuronal calcium influx.
Conclusions:
- The FGFR-PLCgamma cascade is central to neurite outgrowth stimulated by specific CAMs.
- A direct interaction between CAMs and FGFR is suggested by conserved binding motifs.
- This interaction model provides a framework for predicting other CAMs that may interact with FGFR.