Rao, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Grad Sch, 320 Yueyang Rd, Shanghai 200031, Peoples R China,email@example.com
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.
Jiang, H; Guo, W; Liang, XH; Rao, Y.Both the establishment and the maintenance of neuronal polarity require active mechanisms: Critical roles of GSK-3 beta and its upstream regulators,CELL,2005,120(1):123-135