Control of Neuronal Growth Cone Navigation by Asymmetric Inositol 1,4,5-Trisphosphate Signals

Abstract

Inositol 1,4,5-trisphosphate (IP(3)) is generally viewed as a global messenger that increases cytosolic calcium ion (Ca(2+)) concentration. However, the spatiotemporal dynamics of IP(3) and the functional significance of localized IP(3) production in cell polarity remain largely unknown. Here, we demonstrate the critical role of spatially restricted IP(3) signals in axon guidance. We found that IP(3) and ensuing Ca(2+) signals were produced asymmetrically across growth cones exposed to an extracellular gradient of nerve growth factor (NGF) and mediated growth cone turning responses to NGF. Moreover, photolysis-induced production of IP(3) on one side of a growth cone was sufficient to initiate growth cone turning toward the side with the higher concentration of IP(3). Thus, locally produced IP(3) encodes spatial information that polarizes the growth cone for guided migration.