title: Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling.
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.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Beirowski
authors.forename: Jason
authors.initials: J
authors.lastname: Gustin
authors.forename: Sean M
authors.initials: SM
authors.lastname: Armour
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Andreu
authors.initials: A
authors.lastname: Viader
authors.forename: Brian J
authors.initials: BJ
authors.lastname: North
authors.forename: Shaday
authors.initials: S
authors.lastname: Michán
authors.forename: Robert H
authors.initials: RH
authors.lastname: Baloh
authors.forename: Judy P
authors.initials: JP
authors.lastname: Golden
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002853:Chromatography, Liquid; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D017931:DNA Primers; C115084:Pard3 protein, mouse; D008156:Luciferases; C115015:PKC-3 protein; D011493:Protein Kinase C; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2