Fig. 10.

Proposed mechanism underlying LN-mediated growth cone guidance in vitro. Our results suggest that guidance instructions provided by LN-coated beads activate a signaling mechanism composed of two temporally and functionally distinct Ca²⁺ signals that are linked sequentially byCaM, PKC, and CaM-kinase II (CaMK-II). Growth cones establish contact to LN-coated beads with individual filopodia. This adhesion event stimulates in an influx of extracellular Ca²⁺, presumably at adhesion sites between filopodia and LN-coated beads, resulting in a rise of [Ca²⁺]_i(shading adherent filopodia). This early Ca²⁺ signal is required for growth cone turning, together with an activation of downstream targets (arrow), including CaM and PKC (markedinside the growth cone). This is followed by a Ca²⁺/CaM-dependent activation of CaM-kinase II, which regulates both the delayed and sustained rise of [Ca²⁺]_i associated with the period of increased rates of outgrowth (dark shading inside the growth cone).