Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators

Hui Jiang; Wei Guo; Xinhua Liang; Yi Rao

doi:10.1016/j.cell.2004.12.033

Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators

Cell. 2005 Jan 14;120(1):123-35. doi: 10.1016/j.cell.2004.12.033.

Authors

Hui Jiang¹, Wei Guo, Xinhua Liang, Yi Rao

Affiliation

¹ Institute of Neuroscience, Shanghai Institutes of Biological Sciences, The Graduate School, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

PMID: 15652487
DOI: 10.1016/j.cell.2004.12.033

Abstract

Axon-dendrite polarity is a cardinal feature of neuronal morphology essential for information flow. Here we report a differential distribution of GSK-3beta activity in the axon versus the dendrites. A constitutively active GSK-3beta mutant inhibited axon formation, whereas multiple axons formed from a single neuron when GSK-3beta activity was reduced by pharmacological inhibitors, a peptide inhibitor, or siRNAs. An active mechanism for maintaining neuronal polarity was revealed by the conversion of preexisting dendrites into axons upon GSK-3 inhibition. Biochemical and functional data show that the Akt kinase and the PTEN phosphatase are upstream of GSK-3beta in determining neuronal polarity. Our results demonstrate that there are active mechanisms for maintaining as well as establishing neuronal polarity, indicate that GSK-3beta relays signaling from Akt and PTEN to play critical roles in neuronal polarity, and suggest that application of GSK-3beta inhibitors can be a novel approach to promote generation of new axons after neural injuries.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / drug effects
Axons / physiology
Cell Polarity / physiology*
Cells, Cultured
Dendrites / physiology
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors
Glycogen Synthase Kinase 3 / pharmacology
Glycogen Synthase Kinase 3 / physiology*
Glycogen Synthase Kinase 3 beta
Hippocampus / cytology
Mutation
Neurons / enzymology
Neurons / physiology*
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases / physiology
Protein Serine-Threonine Kinases / metabolism
Protein Serine-Threonine Kinases / physiology
Protein Tyrosine Phosphatases / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
RNA, Small Interfering / pharmacology
Rats

Substances

Enzyme Inhibitors
Proto-Oncogene Proteins
RNA, Small Interfering
Akt1 protein, rat
Glycogen Synthase Kinase 3 beta
Gsk3b protein, rat
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
Glycogen Synthase Kinase 3
Phosphoric Monoester Hydrolases
Protein Tyrosine Phosphatases
PTEN Phosphohydrolase
Pten protein, rat