Journal article
α6β4 Integrin and Dystroglycan Cooperate to Stabilize the Myelin Sheath
The Journal of neuroscience, Vol.28(26), pp.6714-6719
06/25/2008
DOI: 10.1523/JNEUROSCI.0326-08.2008
PMCID: PMC2597422
PMID: 18579745
Abstract
Schwann cells integrate signals deriving from the axon and the basal lamina to myelinate peripheral nerves. Integrin α6β4 is a laminin receptor synthesized by Schwann cells and displayed apposed to the basal lamina. α6β4 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, α6β4 integrin binds peripheral myelin protein 22, whose alteration causes the most common demyelinating hereditary neuropathy. All these data suggest a role for α6β4 integrin in peripheral nerve myelination. Here we show that ablating α6β4 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, α6β4 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, α6β4 integrin confers stability to myelin in peripheral nerves.
Details
- Title: Subtitle
- α6β4 Integrin and Dystroglycan Cooperate to Stabilize the Myelin Sheath
- Creators
- Alessandro Nodari - Department of Biological and Technological Research andStefano C Previtali - Institute of Experimental Neurology and Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy, andGabriele Dati - Department of Biological and Technological Research andSimona Occhi - Department of Biological and Technological Research andFelipe A Court - Department of Biological and Technological Research andCristina Colombelli - Department of Biological and Technological Research andDesirée Zambroni - Department of Biological and Technological Research andGiorgia Dina - Institute of Experimental Neurology and Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy, andUbaldo Del Carro - Institute of Experimental Neurology and Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy, andKevin P Campbell - Howard Hughes Medical Institute and Departments of Molecular Physiology and Biophysics, Internal Medicine, and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Angelo Quattrini - Institute of Experimental Neurology and Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy, andLawrence Wrabetz - Department of Biological and Technological Research andM. Laura Feltri - Department of Biological and Technological Research and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.28(26), pp.6714-6719
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.0326-08.2008
- PMID
- 18579745
- PMCID
- PMC2597422
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 06/25/2008
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020884502771
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