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IP3 Points the Way
During nervous system development, neurites navigate to their targets by responding to cues in the environment. Attractive or repulsive turning depends on the generation of asymmetric changes in Ca2+ within the growth cone of the developing neurite. The source of these intracellular Ca2+ signals is critical to determining whether the response is attractive (with the growth cone turning toward the side with increased Ca2+ concentration) or repulsive (with the growth cone turning away from the side with increased Ca2+ concentration). Here, Akiyama et al. show that attractive turning to nerve growth factor (NGF) depends on phospholipase C (PLC)–dependent generation of asymmetric changes in inositol 1,4,5-trisphosphate (IP3) and the ensuing IP3-induced Ca2+ release from the endoplasmic reticulum. Dissection of the pathway showed that the turning response required basal cAMP signaling upstream of asymmetric IP3-induced Ca2+ release and required basal phosphatidylinositol 3-kinase (PI3K)–dependent signaling downstream.
