Control of Neuronal Growth Cone Navigation by Asymmetric Inositol 1,4,5-Trisphosphate Signals
Hiroki Akiyama1,
Toru Matsu-ura2,
Katsuhiko Mikoshiba2, and
Hiroyuki Kamiguchi1*
1 Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
2 Laboratory for Developmental Neurobiology, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan.
Abstract:
Inositol 1,4,5-trisphosphate (IP3) is generally viewed as a global messenger that increases cytosolic calcium ion (Ca2+) concentration. However, the spatiotemporal dynamics of IP3 and the functional significance of localized IP3 production in cell polarity remain largely unknown. Here, we demonstrate the critical role of spatially restricted IP3 signals in axon guidance. We found that IP3 and ensuing Ca2+ 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 IP3 on one side of a growth cone was sufficient to initiate growth cone turning toward the side with the higher concentration of IP3. Thus, locally produced IP3 encodes spatial information that polarizes the growth cone for guided migration.
* To whom correspondence should be addressed. E-mail: kamiguchi{at}brain.riken.jp
