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Updated: Jun 21, 2026

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance
Published on: October 21, 2021
Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals
Hiroki Akiyama1, Toru Matsu-ura, Katsuhiko Mikoshiba
1Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan.
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.
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