STRAD pseudokinases regulate axogenesis and LKB1 stability

Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Reilly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.Results: We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.Conclusions: We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.

Original languageEnglish (US)
Article number5
JournalNeural Development
Volume9
Issue number1
DOIs
StatePublished - Mar 4 2014

Keywords

  • Axon
  • LKB1
  • Neurodevelopment
  • Pseudokinase
  • STRAD

ASJC Scopus subject areas

  • Developmental Neuroscience

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    Veleva-Rotse, B. O., Smart, J. L., Baas, A. F., Edmonds, B., Zhao, Z. M., Brown, A., Klug, L. R., Hansen, K., Reilly, G., Gardner, A. P., Subbiah, K., Gaucher, E. A., Clevers, H., & Barnes, A. P. (2014). STRAD pseudokinases regulate axogenesis and LKB1 stability. Neural Development, 9(1), [5]. https://doi.org/10.1186/1749-8104-9-5