Publication Date:
2011-03-26
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325765/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325765/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amato, Stephen -- Liu, Xiuxin -- Zheng, Bin -- Cantley, Lewis -- Rakic, Pasko -- Man, Heng-Ye -- GM41890/GM/NIGMS NIH HHS/ -- GM56203/GM/NIGMS NIH HHS/ -- K99CA133245/CA/NCI NIH HHS/ -- MH07907/MH/NIMH NIH HHS/ -- R00 CA133245/CA/NCI NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 NS014841/NS/NINDS NIH HHS/ -- R01 NS014841-32/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 8;332(6026):247-51. doi: 10.1126/science.1201678. Epub 2011 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436401" target="_blank"〉PubMed〈/a〉
Keywords:
AMP-Activated Protein Kinases/*metabolism
;
Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
;
Animals
;
Axons/enzymology/*physiology/ultrastructure
;
*Cell Polarity/drug effects
;
Cells, Cultured
;
Hippocampus/cytology/embryology
;
Metformin/pharmacology
;
Mice
;
Microtubule-Associated Proteins/metabolism
;
Neurons/cytology/drug effects/enzymology/*physiology
;
Phosphatidylinositol 3-Kinase/*metabolism
;
Phosphorylation
;
Proto-Oncogene Proteins c-akt/metabolism
;
Rats
;
Recombinant Fusion Proteins/metabolism
;
Ribonucleotides/pharmacology
;
Signal Transduction
;
Tissue Culture Techniques
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
