Format

Send to

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

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

Author information

1
Department of Neurology and Program in Neurosciences, University of California, San Francisco, California 94158, USA.
2
1] Department of Pediatrics, Brain Cancer Center, Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229 [2] Department of Pediatrics and Obstetrics/Gynecology, State Key Laboratory of Biotherapy, Cancer Center, West China Second Hospital, Sichuan University, Chengdu 61004, China.
3
Department of Ophthalmology and Physiology and Programs in Neurosciences, University of California, San Francisco, California 94143, USA.
4
Department of Pediatrics, Brain Cancer Center, Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
5
Department of Cellular Neurobiology, Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.

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.

PMID:
25255972
PMCID:
PMC4334370
DOI:
10.1038/ncomms5991
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center