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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Sirt2Ratmyelination in peripheral nervous system involved_inIMP PMID:21949390UniProt 
Sirt2Ratprotein deacetylation involved_inIMP PMID:21949390UniProt 
Sirt2Ratregulation of myelination involved_inIMP PMID:21949390UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Sirt2Ratlateral loop located_inIDA PMID:21949390UniProt 
Sirt2Ratparanodal junction located_inIDA PMID:21949390UniProt 
Sirt2RatSchmidt-Lanterman incisure located_inIDA PMID:21949390UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Sirt2  (sirtuin 2)


Additional Information