Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent

Yun An A Shen, Yan Chen, Dang Q. Dao, Sonia R. Mayoral, Laiman Wu, Dies Meijer, Erik M. Ullian, Jonah R. Chan, Q. Richard Lu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The Schwann cell (SC)-axon interface represents a membrane specialization that integrates axonal signals to coordinate cytoskeletal dynamics resulting in myelination. Here we show that LKB1/Par-4 is asymmetrically localized to the SC-axon interface and co-localizes with the polarity protein Par-3. Using purified SCs and myelinating cocultures, we demonstrate that localization is dependent on the phosphorylation of LKB1 at serine-431. SC-specific deletion of LKB1 significantly attenuates developmental myelination, delaying the initiation and altering the myelin extent into adulthood, resulting in a 30% reduction in the conduction velocity along the adult sciatic nerves. Phosphorylation of LKB1 by protein kinase A is essential to establish the asymmetric localization of LKB1 and Par-3 and rescues the delay in myelination observed in the SC-specific knockout of LKB1. Our findings suggest that SC polarity may coordinate multiple signalling complexes that couple SC-axon contact to the redistribution of specific membrane components necessary to initiate and control myelin extent.

Original languageEnglish (US)
Article number4991
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shen, Y. A. A., Chen, Y., Dao, D. Q., Mayoral, S. R., Wu, L., Meijer, D., Ullian, E. M., Chan, J. R., & Lu, Q. R. (2014). Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent. Nature communications, 5, [4991]. https://doi.org/10.1038/ncomms5991