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The Journal of Neuroscience, June 25, 2008, 28(26):6714-6719; doi:10.1523/JNEUROSCI.0326-08.2008

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Brief Communications
6β4 Integrin and Dystroglycan Cooperate to Stabilize the Myelin Sheath

Alessandro Nodari,¹ Stefano C. Previtali,² Gabriele Dati,¹ Simona Occhi,¹ Felipe A. Court,¹ Cristina Colombelli,¹ Desirée Zambroni,¹ Giorgia Dina,² Ubaldo Del Carro,² Kevin P. Campbell,³ Angelo Quattrini,² Lawrence Wrabetz,¹ and M. Laura Feltri¹

¹Department of Biological and Technological Research and ²Institute of Experimental Neurology and Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy, and ³Howard Hughes Medical Institute and Departments of Molecular Physiology and Biophysics, Internal Medicine, and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242

Correspondence should be addressed to M. Laura Feltri, Department of Biological and Technological Research, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Email: feltri.laura{at}hsr.it

Schwann cells integrate signals deriving from the axon and the basal lamina to myelinate peripheral nerves. Integrin 6β4 is a laminin receptor synthesized by Schwann cells and displayed apposed to the basal lamina. 6β4 integrin expression in Schwann cells is induced by axons at the onset of myelination, and rises in adulthood. The β4 chain has a uniquely long cytoplasmic domain that interacts with intermediate filaments such as dystonin, important in peripheral myelination. Furthermore, 6β4 integrin binds peripheral myelin protein 22, whose alteration causes the most common demyelinating hereditary neuropathy. All these data suggest a role for 6β4 integrin in peripheral nerve myelination. Here we show that ablating 6β4 integrin specifically in Schwann cells of transgenic mice does not affect peripheral nerve development, myelin formation, maturation, or regeneration. However, consistent with maximal expression in adult nerves, 6β4 integrin-null myelin is more prone to abnormal folding with aging. When the laminin receptor dystroglycan is also ablated, major folding abnormalities occur, associated with acute demyelination in some peripheral nervous system districts. These data indicate that, similar to its role in skin, 6β4 integrin confers stability to myelin in peripheral nerves.

Key words: 6β4 integrin; dystroglycan; myelin; Schwann cells; targeted mutagenesis; peripheral nervous system

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Received Jan. 24, 2008; revised May 23, 2008; accepted May 27, 2008.

Correspondence should be addressed to M. Laura Feltri, Department of Biological and Technological Research, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Email: feltri.laura{at}hsr.it

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Myelin-related mutants identify high vulnerability of the near-nodal compartment of nerve fibers

Rudolf Martini

J. Neurosci. Online, 27 Jun 2008 [Full text]

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