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Friday, December 08, 2006

Bimodality of calcium dependent axon pathfinding

The growth cone is a motile structure at the tip of the axon that guides axon outgrowth. It can detect the presence of various molecules that will either attract or repel the growing axon. Somehow the receptors in the growth cone activate pathways that result in a change in the local cytoskeleton and adhesive ability of the growth cone. Calcium is an important mediator in this pathway. In this article (link goes to abstract in PubMed), Gomez and Zheng reviewed research on the role of calcium in axon pathfinding. The article explained how calcium signals are bimodal: they seem to stimulate certain processes and inhibit the same processes. It’s interesting that a single simple ion can signal the growth cone to produce opposing motile behaviors. Although calcium influx tends to repulse the growth cone and calcium outflow tends to attract it, it’s not the absolute calcium concentration that really guides the growth cone, it’s the change in local concentration relative to the baseline that affects morphology. Calcium can change the way that the cell responds to a particular factor such as netrin. The chemoattraction of the growth cone to netrin can be reversed to repulsion when certain calcium channels are blocked. Calcium signaling pathways are also involved in the branching pattern of the axon and dendrites. Branching factors work through calcium activated pathways to expand branches while other factors eliminate branches by activating other calcium signals, again bimodal. This can work because a distinct signal is used for each process.
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