Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 43, Pages E952-E961Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1104969108
Keywords
neuropathy; sirtuin; acetylation
Categories
Funding
- National Institutes of Health Neuroscience Blueprint Center [P30 NS057105]
- Hope Center for Neurological Disorders
- National Institutes of Health [NS040745, AG13730, DK59820, AG027916, AG028730, DK19645, NS055980, R21NS059566]
- Fondation Recherche Medicale
- Swiss National Science Foundation [31003A-124713/1]
- European Research Council [2008-AdG-23118]
- Ellison Medical Foundation
- Glenn Medical Foundation
- European Molecular Biology Organization
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The formation of myelin by Schwann cells (SCs) occurs via a series of orchestrated molecular events. We previously used global expression profiling to examine peripheral nerve myelination and identified the NAD(+)-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination. Here, we show that Sirt2 expression in SCs is correlated with that of structural myelin components during both developmental myelination and remyelination after nerve injury. Transgenic mice lacking or overexpressing Sirt2 specifically in SCs show delays in myelin formation. In SCs, we found that Sirt2 deacetylates Par-3, a master regulator of cell polarity. The deacetylation of Par-3 by Sirt2 decreases the activity of the polarity complex signaling component aPKC, thereby regulating myelin formation. These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity.
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