The Calcium Cue to Turn

Abstract

Calcium regulates neuronal growth cone extension, but its precise role in steering growth cones in a particular direction has not been clear. Zheng and Hong et al . now report that a localized increase in intracellular calcium within the growth cone may provide a directional signal that is sufficient to initiate both attractive and repulsive responses to extracellular cues. By spatially restricting elevations in intracellular calcium through focal laser-induced photolysis (FLIP) of caged calcium, Zheng observed that Xenopus neuronal growth cones turned in the direction of increased calcium. In contrast to this attractive response, focal elevation of intracellular calcium induced repulsion when extracellular and global intracellular calcium concentrations were decreased. It could be that opposite turning responses reflect modulation of different signaling molecules that have different thresholds of activation by intracellular calcium. Hong et al. also observed these effects through fluorescence imaging of intracellular calcium in Xenopus neurons. When exposed to low-dose gradients of extracellular ryanodine, calcium release from intracellular stores was triggered, stimulating growth cone turning towards the region of higher intracellular calcium (in closest proximity to the ryanodine source). Intermediate concentrations of ryanodine induced both attractive and repulsive responses. Hong et al. propose that extracellular cues such as netrin may activate the release of calcium from intracellular stores, producing a calcium gradient across the growth cone. Steep and shallow gradients may alter the cytokeleton and lead to attractive or repulsive responses, respectively. Zheng, J.Q. (2000) Turning of nerve growth cones induced by localized increases in intracellular calcium ions. Nature 403 : 89-93. [Online Journal] Hong, K., Nishiyama, M., Henley, J., Tessier-Lavigne, M., and Poo, M-m. (2000) Calcium signalling in the guidance of nerve growth by netrin-1. Nature 403 : 93-98. [Online Journal]