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Science 332 (6026): 247-251

Copyright © 2011 by the American Association for the Advancement of Science

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

Stephen Amato,1 Xiuxin Liu,2,* Bin Zheng,3,4,* Lewis Cantley,3,4 Pasko Rakic,2 Heng-Ye Man1,{dagger}

Abstract: 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. We found that activation of the energy-sensing adenosine 5'-monophosphate (AMP)–activated protein kinase (AMPK) pathway suppressed axon initiation and neuronal polarization. Phosphorylation of the kinesin light chain of the Kif5 motor protein by AMPK disrupted the association of the motor with phosphatidylinositol 3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting polarization and axon growth.

1 Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
2 Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
3 Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
4 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: hman{at}bu.edu


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