Review: A Role for the FGF Receptor in the Axonal Growth Response Stimulated by Cell Adhesion Molecules?

Abstract

Cell adhesion molecules (CAMs) have been shown to stimulate axonal growth. The molecular basis of this response has been extensively studied and a range of agents that promote or inhibit CAM stimulated axonal growth have now been identified. These studies have led to the suggestion that following homophilic and/or heterophilic interactions CAM specific signal transduction pathways are activated which are directly responsible for promotion of axonal growth. In this review we will suggest that the axonal growth response stimulated by three CAMs (NCAM, N-cadherin and L1) can be operationally divided into a number of phases. During the first phase homophilic and/or heterophilic binding between the CAMs expressed on the axonal growth cone and cellular substrate take place. This is followed by an interaction of the neuronal CAMs with the fibroblast growth factor receptor (FGFR), leading to receptor activation by autophosphorylation. This results in the recruitment and activation of additional effector molecules via interactions of their SH2 domains with the activated receptor. In this context the key event in terms of neurite outgrowth appears to be the activation of phospholipase C gamma (PLCγ) which sets into motion a second messenger cascade that ultimately leads to a modification, most likely by phosphorylation, of cytoskeletal elements that are involved in growth cone motility.

Key Words:

• signal transduction
• cell adhesion molecules
• fibroblast growth factor
• receptor protein tyrosine kinase
• neurite outgrowth