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 language | English |
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Article number | 4991 |
Number of pages | 11 |
Journal | Nature Communications |
Volume | 5 |
DOIs | |
Publication status | Published - 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