Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating α-tubulin
Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating α-tubulin
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DOI：
10.1523/jneurosci.4181-06.2007
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发表时间：
2007-03-07
影响因子：
5.3
通讯作者：
Liang, Fengyi
中科院分区：
文献类型：
--
作者：
Li, Wenbo;Zhang, Bin;Liang, Fengyi
沉默信息调节因子-2（SIR 2）蛋白调节多种生物体的寿命，但其在中枢神经系统中的分布和作用尚不清楚。在这里，我们表明，sirtuin 2（SIRT 2），哺乳动物SIR 2同源物，是一个少突胶质细胞胞质蛋白和本地化的外环和髓磷脂鞘。在OLN-93少突胶质细胞的胞质蛋白中，α-微管蛋白是SIRT 2脱乙酰酶的主要底物。在培养的原代少突胶质细胞前体（OLP）中，SIRT 2的出现伴随着α-微管蛋白乙酰化的升高和OLP分化为早熟阶段。SIRT 2的小干扰RNA敲低增加了OLP的α-微管蛋白乙酰化、髓鞘碱性蛋白表达和细胞乔木复杂性。SIRT 2过表达具有相反的作用，并抵消了过表达的曲坦诺丁的细胞树枝化促进作用。SIRT 2突变同时降低了其脱乙酰酶活性及其对OLP树枝化的阻碍作用。这些结果证明了SIRT 2对微管蛋白乙酰化对少突胶质细胞分化的促进作用的平衡作用。少突胶质细胞选择性SIRT 2的可用性可能对髓鞘形成，髓鞘-轴突相互作用和脑老化具有重要意义。
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.