Abstract:

Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission. Given this incredible importance, calcium ions are tightly controlled by a host of molecular players including ion channels, sensors and buffering proteins. Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect, for example by altering nuclear histones which can lead to changes in gene transcription. All of these mechanisms come into play in developing axons as calcium is required for both axon pathfinding and branching. Furthermore, after neuronal injury, waves of calcium originating at the site of axon segmentation and propagating to the nucleus have long been known to be required for regeneration. These changes in intracellular calcium concentrations [Ca2+]i must be properly controlled or else new growth cones may fail to form and degeneration of the neuron may occur. While many of the molecular players involved in these calcium-dependent processes have been identified, calcium buffering proteins have often been undervalued for their role in regulating axon growth either during normal development or in the event of injury.