title: AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization.
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.
authors: Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
authors: Stephen
authors: S
authors: Amato
authors: Xiuxin
authors: X
authors: Liu
authors: Bin
authors: B
authors: Zheng
authors: Lewis
authors: L
authors: Cantley
authors: Pasko
authors: P
authors: Rakic
authors: Heng-Ye
authors: HY
authors: Man
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D016547:Kinesins; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D016547:Kinesins; C031143:AICA ribonucleotide