AMP-Activated Protein Kinase Regulates Neuronal Polarization by Interfering with PI 3-Kinase Localization

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Science  24 Mar 2011:
DOI: 10.1126/science.1201678


Axon-dendrite polarization is crucial for neural network wiring and information processing in the brain. Polarization begins with the transformation of a single neurite into an axon and its subsequent rapid extension, which requires coordination of cellular energy status to allow for transport of building materials to support axon growth. Here, we found that activation of the energy-sensing AMP-activated protein kinase (AMPK) pathway suppressed axon initiation and neuronal polarization. Phosphorylation of the kinesin light chain (KLC) of the Kif5 motor protein by AMPK disrupted the association of the motor with PI3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting polarization and axon growth.

  • * These authors contributed equally to this work.