Signal amplification in growth cone gradient sensing by a double negative feedback loop among PTEN, PI(3,4,5)P₃ and actomyosin.

ABSTRACT: Axon guidance during neural wiring involves a series of precisely controlled chemotactic events by the motile axonal tip, the growth cone. A fundamental question is how neuronal growth cones make directional decisions in response to extremely shallow gradients of guidance cues with exquisite sensitivity. Here we report that nerve growth cones possess a signal amplification mechanism during gradient sensing process. In neuronal growth cones of Xenopus spinal neurons, phosphatidylinositol-3,4,5-trisphosphate (PIP₃), an important signaling molecule in chemotaxis, was actively recruited to the up-gradient side in response to an external gradient of brain-derived neurotrophic factor (BDNF), resulting in an intracellular gradient with approximate 30-fold amplification of the input. Fu

SUBMITTER: Li X 

PROVIDER: S-EPMC9856701 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature