Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance

Hiroki Akiyama, Hiroyuki Kamiguchi*

*この研究の対応する著者

研究成果査読

31 被引用数 (Scopus)

抄録

The activity of PI3K is necessary for polarized cell motility. To guide extending axons, environmental cues polarize the growth cone via asymmetric generation of Ca2+ signals and subsequent intracellular mechanical events, including membrane trafficking and cytoskeletal reorganization. However, it remains unclear how PI3K is involved in such events for axon guidance. Here, we demonstrate that PI3K plays a permissive role in growth cone turning by facilitating microtubule (MT)- dependent membrane transport. Using embryonic chick dorsal root ganglion neurons in culture, attractive axon turning was induced by Ca2+ elevations on one side of the growth cone by photolyzing caged Ca2+ or caged inositol 1,4,5-trisphosphate. We show that PI3K activity was required downstream of Ca2+ signals for growth cone turning. Attractive Ca2+ signals, generated with caged Ca2+ or caged inositol 1,4,5-trisphosphate, triggered asymmetric transport of membrane vesicles from the center to the periphery of growth cones in a MT-dependent manner. This centrifugal vesicle transport was abolished by PI3K inhibitors, suggesting that PI3K is involved in growth cone attraction at the level of membrane trafficking. Consistent with this observation, immunocytochemistry showed that PI3K inhibitors reduced MTs in the growth cone peripheral domain. Time-lapse imaging of EB1 on the plus-end of MTs revealed that MT advance into the growth cone peripheral domain was dependent on PI3K activity: inhibition of the PI3K signaling pathway attenuated MT advance, whereas exogenous phosphatidylinositol 3,4,5-trisphosphate, the product of PI3Kcatalyzed reactions, promoted MT advance. This study demonstrates the importance of PI3K-dependent membrane trafficking in chemotactic cell migration.

本文言語English
ページ(範囲)41740-41748
ページ数9
ジャーナルJournal of Biological Chemistry
285
53
DOI
出版ステータスPublished - 2010 12 31
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞生物学
  • 分子生物学

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