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Lck tyrosine kinase mediates β1-integrin signalling to regulate Schwann cell migration and myelination.
- Source :
-
Nature communications [Nat Commun] 2013; Vol. 4, pp. 1912. - Publication Year :
- 2013
-
Abstract
- The interaction between laminin and β1-integrin on the surface of Schwann cells regulates Schwann cell proliferation, maturation and differentiation. However, the signalling mediators that fine-tune these outcomes are not fully elucidated. Here we show that lymphoid cell kinase is the crucial effector of β1-integrin signalling in Schwann cells. Lymphoid cell kinase is activated after laminin treatment of Schwann cells, while downregulation of β1-integrin with short interfering RNAs inhibits lymphoid cell kinase phosphorylation. Treatment of Schwann cells with a selective lymphoid cell kinase inhibitor reveals a pathway that involves paxillin and CrkII, which ultimately elevates Rac-GTP levels to induce radial lamellipodia formation. Inhibition of lymphoid cell kinase in Schwann cell-dorsal root ganglion cocultures and dorsal root ganglions from Lck(-/-) mice show a reduction of Schwann cell longitudinal migration, reduced myelin formation and internode length. Finally, Lck(-/-) mice exhibit delays in myelination, thinner myelin with abnormal g-ratios and aberrant myelin outfoldings. Our data implicate lymphoid cell kinase as a major regulator of cytoskeletal dynamics, migration and myelination in the peripheral nervous system.
- Subjects :
- Animals
Axons drug effects
Axons metabolism
Coculture Techniques
Ganglia, Spinal cytology
Ganglia, Spinal metabolism
Humans
Laminin pharmacology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) antagonists & inhibitors
Mice
Mice, Inbred C57BL
Myelin Sheath drug effects
Organic Cation Transport Proteins metabolism
Paxillin metabolism
Phosphorylation drug effects
Protein Binding drug effects
Proto-Oncogene Proteins c-crk metabolism
Pseudopodia drug effects
Pseudopodia metabolism
Rats
Schwann Cells drug effects
Sciatic Nerve drug effects
Sciatic Nerve metabolism
Sciatic Nerve pathology
Sciatic Nerve ultrastructure
rac GTP-Binding Proteins metabolism
Cell Movement drug effects
Integrin beta1 metabolism
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism
Myelin Sheath metabolism
Schwann Cells cytology
Schwann Cells enzymology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 23715271
- Full Text :
- https://doi.org/10.1038/ncomms2928