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

Nat Commun. 2014 Sep 26;5:4991. doi: 10.1038/ncomms5991.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins
  • Cell Polarity*
  • Cells, Cultured
  • Mice
  • Mice, Knockout
  • Myelin Sheath / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Schwann Cells / cytology*
  • Schwann Cells / enzymology*
  • Schwann Cells / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Pard3 protein, mouse
  • Stk11 protein, mouse
  • Protein-Serine-Threonine Kinases