LKB1 and SAD Kinases Define a Pathway Required for the Polarization of Cortical Neurons

Anthony P. Barnes, Brendan N. Lilley, Y. Albert Pan, Lisa J. Plummer, Ashton W. Powell, Alexander N. Raines, Joshua R. Sanes, Franck Polleux

Research output: Contribution to journalArticle

287 Scopus citations

Abstract

The polarization of axon and dendrites underlies the ability of neurons to integrate and transmit information in the brain. We show here that the serine/threonine kinase LKB1, previously implicated in the establishment of epithelial polarity and control of cell growth, is required for axon specification during neuronal polarization in the mammalian cerebral cortex. LKB1 polarizing activity requires its association with the pseudokinase Stradα and phosphorylation by kinases such as PKA and p90RSK, which transduce neurite outgrowth-promoting cues. Once activated, LKB1 phosphorylates and thereby activates SAD-A and SAD-B kinases, which are also required for neuronal polarization in the cerebral cortex. SAD kinases, in turn, phosphorylate effectors such as microtubule-associated proteins that implement polarization. Thus, we provide evidence in vivo and in vitro for a multikinase pathway that links extracellular signals to the intracellular machinery required for axon specification.

Original languageEnglish (US)
Pages (from-to)549-563
Number of pages15
JournalCell
Volume129
Issue number3
DOIs
StatePublished - May 4 2007

Keywords

  • CELLBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Barnes, A. P., Lilley, B. N., Pan, Y. A., Plummer, L. J., Powell, A. W., Raines, A. N., Sanes, J. R., & Polleux, F. (2007). LKB1 and SAD Kinases Define a Pathway Required for the Polarization of Cortical Neurons. Cell, 129(3), 549-563. https://doi.org/10.1016/j.cell.2007.03.025