Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin.
Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, alpha-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated alpha-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the alpha-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on oligodendroglial differentiation. Selective SIRT2 availability to oligodendroglia may have important implications for myelinogenesis, myelin-axon interaction, and brain aging.
Li
Wenbo
W
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Zhang
Bin
B
Tang
Junhong
J
Cao
Qiong
Q
Wu
Yajun
Y
Wu
Chun
C
Guo
Jing
J
Ling
Eng-Ang
EA
Liang
Fengyi
F
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D002490:Central Nervous System / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases; D009186:Myelin Sheath / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C097475:Sirt2 protein, rat; D014404:Tubulin; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases