Filopodial Calcium Transients Promote Substrate-Dependent Growth Cone Turning

Abstract

Filopodia that extend from neuronal growth cones sample the environment for extracellular guidance cues, but the signals they transmit to growth cones are unknown. Filopodia were observed generating localized transient elevations of intracellular calcium ([Ca 2+ ] i ) that propagate back to the growth cone and stimulate global Ca 2+ elevations. The frequency of filopodial Ca 2+ transients was substrate-dependent and may be due in part to influx of Ca 2+ through channels activated by integrin receptors. These transients slowed neurite outgrowth by reducing filopodial motility and promoted turning when stimulated differentially within filopodia on one side of the growth cone. These rapid signals appear to serve both as autonomous regulators of filopodial movement and as frequency-coded signals integrated within the growth cone and could be a common signaling process for many motile cells.