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.
journal_name
Proc Natl Acad Sci U S Aauthors
Beirowski B,Gustin J,Armour SM,Yamamoto H,Viader A,North BJ,Michán S,Baloh RH,Golden JP,Schmidt RE,Sinclair DA,Auwerx J,Milbrandt Jdoi
10.1073/pnas.1104969108subject
Has Abstractpub_date
2011-10-25 00:00:00pages
E952-61issue
43eissn
0027-8424issn
1091-6490pii
1104969108journal_volume
108pub_type
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