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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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
Article number4991
Number of pages11
JournalNature Communications
Volume5
DOIs
Publication statusPublished - Sept 2014

Keywords / Materials (for Non-textual outputs)

  • DEPENDENT PROTEIN-KINASE
  • REGULATES SPINDLE ORIENTATION
  • PERIPHERAL NERVOUS-SYSTEM
  • C-ELEGANS EMBRYO
  • OLIGODENDROCYTE DIFFERENTIATION
  • DROSOPHILA NEUROBLASTS
  • ASYMMETRIC DIVISIONS
  • NEURONAL POLARITY
  • PLANAR DIVISIONS
  • CNS MYELINATION

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