1. Academic Validation
  2. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling

Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling

  • Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E952-61. doi: 10.1073/pnas.1104969108.
Bogdan Beirowski 1 Jason Gustin Sean M Armour Hiroyasu Yamamoto Andreu Viader Brian J North Shaday Michán Robert H Baloh Judy P Golden Robert E Schmidt David A Sinclair Johan Auwerx Jeffrey Milbrandt
Affiliations

Affiliation

  • 1 Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Abstract

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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