The generation of localized calcium rises mediated by cell adhesion molecules and their role in neuronal growth cone motility.
Neurite growth and guidance depends on the transduction of extracellular guidance cues into motile responses by the sensory apparatus at the tip of the neurite, the growth cone. Contact of the growth cone with extracellular ligands leads to the cytoskeletal reorganisation required for changes in rate of motility and direction of outgrowth. Differential adhesion mediated by cell adhesion molecules and signal transduction pathways mediated by growth cone receptors were once seen as separate but cooperative events in controlling growth cone motility. However, recent findings suggest that cell adhesion molecules can activate novel signalling pathways in the growth cone by the recruitment of fibroblast growth factor receptors leading to neurite outgrowth. This Review focuses on work by various laboratories centering on the intracellular consequences of the cell adhesion molecule-mediated activation of the fibroblast growth factor receptor. These include activation of a lipase cascade including phospholipase C and diacylglycerol lipase and culminating in the release of arachidonic acid. This release of arachidonic acid is proposed to activate the transient opening of voltage dependent ion-channels leading to localised rises in growth Ca(2+). Recent findings demonstrating this previously undetectable rise in Ca(2+) in the growth cone are discussed in light of the proposed roles and mechanisms of Ca(2+) in controlling neurite outgrowth. The Ca(2+) rises are thought to induce the activation of GAP43 and Ca(2+)/calmodulin-dependent kinase II, molecules implicated in the modulation of cytoskeletal remodelling. The evidence that this pathway may be involved in the guidance of retinal ganglion cells is evaluated.
Dunican
D J
DJ
Molecular Neurobiology Group, New Hunts House, Kings College London, 4th Floor South Wing, Guy's Campus, London, SE1 9RT, United Kingdom.
Doherty
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism*; D008954:Models, Biological; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D002118:Calcium