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

Author

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  • Yun-An A. Shen

    (University of California)

  • Yan Chen

    (Brain Cancer Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center
    State Key Laboratory of Biotherapy, Cancer Center, West China Second Hospital, Sichuan University)

  • Dang Q. Dao

    (University of California)

  • Sonia R. Mayoral

    (University of California)

  • Laiman Wu

    (Brain Cancer Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center)

  • Dies Meijer

    (Centre for Neuroregeneration, University of Edinburgh)

  • Erik M. Ullian

    (University of California)

  • Jonah R. Chan

    (University of California)

  • Q. Richard Lu

    (Brain Cancer Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center)

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.

Suggested Citation

  • 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, 2014. "Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5991
    DOI: 10.1038/ncomms5991
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