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PMID:18268107

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Citation

Witte, H, Neukirchen, D and Bradke, F (2008) Microtubule stabilization specifies initial neuronal polarization. J. Cell Biol. 180:619-32

Abstract

Axon formation is the initial step in establishing neuronal polarity. We examine here the role of microtubule dynamics in neuronal polarization using hippocampal neurons in culture. We see increased microtubule stability along the shaft in a single neurite before axon formation and in the axon of morphologically polarized cells. Loss of polarity or formation of multiple axons after manipulation of neuronal polarity regulators, synapses of amphids defective (SAD) kinases, and glycogen synthase kinase-3beta correlates with characteristic changes in microtubule turnover. Consistently, changing the microtubule dynamics is sufficient to alter neuronal polarization. Application of low doses of the microtubule-destabilizing drug nocodazole selectively reduces the formation of future dendrites. Conversely, low doses of the microtubule-stabilizing drug taxol shift polymerizing microtubules from neurite shafts to process tips and lead to the formation of multiple axons. Finally, local stabilization of microtubules using a photoactivatable analogue of taxol induces axon formation from the activated area. Thus, local microtubule stabilization in one neurite is a physiological signal specifying neuronal polarization.

Links

PubMed PMC2234250 Online version:10.1083/jcb.200707042

Keywords

Animals; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cell Polarity/drug effects; Cell Polarity/physiology; Cells, Cultured; Central Nervous System/embryology; Central Nervous System/metabolism; Central Nervous System/ultrastructure; Glycogen Synthase Kinase 3/genetics; Glycogen Synthase Kinase 3/metabolism; Glycogen Synthase Kinase 3 beta; Growth Cones/drug effects; Growth Cones/metabolism; Growth Cones/ultrastructure; Hippocampus/embryology; Hippocampus/metabolism; Hippocampus/ultrastructure; Intercellular Signaling Peptides and Proteins/metabolism; Mice; Mice, Knockout; Microtubules/drug effects; Microtubules/metabolism; Microtubules/ultrastructure; Neurites/drug effects; Neurites/metabolism; Neurites/ultrastructure; Neurons/drug effects; Neurons/metabolism; Neurons/ultrastructure; Nocodazole/pharmacology; Paclitaxel/analogs & derivatives; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Rats; Tubulin Modulators/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GSK3B

involved_in

GO:0030011: maintenance of cell polarity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

HUMAN:GSK3B

involved_in

GO:0030010: establishment of cell polarity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:BRSK1

involved_in

GO:0010975: regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q69Z98

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:BRSK1

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q69Z98

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:BRSK1

involved_in

GO:0090176: microtubule cytoskeleton organization involved in establishment of planar polarity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q69Z98

P

Seeded From UniProt

complete

MOUSE:BRSK2

involved_in

GO:0010975: regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q5RJI5

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:BRSK2

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q5RJI5

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:BRSK2

involved_in

GO:0090176: microtubule cytoskeleton organization involved in establishment of planar polarity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q5RJI5

P

Seeded From UniProt

complete

HUMAN:BRSK2

involved_in

GO:2000807: regulation of synaptic vesicle clustering

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRSK1

involved_in

GO:2000807: regulation of synaptic vesicle clustering

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSK3B

involved_in

GO:0030011: maintenance of cell polarity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

occurs_in:(CL:0000540)

Seeded From UniProt

complete

HUMAN:GSK3B

involved_in

GO:0030010: establishment of cell polarity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

occurs_in:(CL:0000540)

Seeded From UniProt

complete

RAT:GSK3B

involved_in

GO:0070507: regulation of microtubule cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(GO:0030424)
  • regulates_o_occurs_in:(CL:0002608)

Seeded From UniProt

complete

RAT:GSK3B

involved_in

GO:1901984: negative regulation of protein acetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0002608)
  • regulates_o_occurs_in:(GO:0015630)

Seeded From UniProt

complete

Notes

See also

References

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