RGD Reference Report - Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. - Rat Genome Database

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

Authors: Beirowski, B  Gustin, J  Armour, SM  Yamamoto, H  Viader, A  North, BJ  Michan, S  Baloh, RH  Golden, JP  Schmidt, RE  Sinclair, DA  Auwerx, J  Milbrandt, J 
Citation: Beirowski B, etal., Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E952-61. doi: 10.1073/pnas.1104969108. Epub 2011 Sep 26.
RGD ID: 8655533
Pubmed: PMID:21949390   (View Abstract at PubMed)
PMCID: PMC3203793   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1104969108   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myelination in peripheral nervous system involved_inIMP 8655533PMID:21949390UniProt 
regulation of myelination involved_inIMP 8655533PMID:21949390UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lateral loop located_inIDA 8655533PMID:21949390UniProt 
paranodal junction located_inIDA 8655533PMID:21949390UniProt 
Schmidt-Lanterman incisure located_inIDA 8655533PMID:21949390UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Sirt2  (sirtuin 2)

Additional Information