Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent.
Nat Commun
; 5: 4991, 2014 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-25255972
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células de Schwann
/
Polaridade Celular
/
Proteínas Serina-Treonina Quinases
/
Bainha de Mielina
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article