Lck tyrosine kinase mediates β1-integrin signalling to regulate Schwann cell migration and myelination

Jennifer K. Ness, Kristin M. Snyder and Nikos Tapinos ()
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Jennifer K. Ness: Molecular Neuroscience Laboratory, Weis Center for Research, Geisinger Clinic
Kristin M. Snyder: Molecular Neuroscience Laboratory, Weis Center for Research, Geisinger Clinic
Nikos Tapinos: Molecular Neuroscience Laboratory, Weis Center for Research, Geisinger Clinic

Nature Communications, 2013, vol. 4, issue 1, 1-14

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2928

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