Filopodial calcium transients promote substrate-dependent growth cone turning

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 elevat ions of intracellular calcium ([Ca2+](i)) that propagate back to the growth cone and stimulate global Ca2+ elevations, The frequency of filopodial Ca2 + transients was substrate-dependent and may be due in part to influx of Ca 2+ through channels activated by integrin receptors. These transients slowe d neurite outgrowth by reducing filopodial motility and promoted turning wh en stimulated differentially within filopodia on one side of the growth con e. These rapid signals appear to serve both as autonomous regulators of fil opodial movement and as frequency-coded signals integrated within the growt h cone and could be a common signaling process for many motile cells.