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The Journal of Neuroscience, March 7, 2007, 27(10):2606-2616; doi:10.1523/JNEUROSCI.4181-06.2007

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Development/Plasticity/Repair
Sirtuin 2, a Mammalian Homolog of Yeast Silent Information Regulator-2 Longevity Regulator, Is an Oligodendroglial Protein That Decelerates Cell Differentiation through Deacetylating -Tubulin

Wenbo Li, Bin Zhang, Junhong Tang, Qiong Cao, Yajun Wu, Chun Wu, Jing Guo, Eng-Ang Ling, and Fengyi Liang

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597

Correspondence should be addressed to Dr. Fengyi Liang, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. Email: antlfy{at}nus.edu.sg

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, -tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated -tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the -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.

Key words: sirtuin 2; tubulin acetylation/deacetylation; oligodendrocyte differentiation; myelination; RNA interference; cytoskeleton

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Received Sept. 25, 2006; revised Dec. 27, 2006; accepted Jan. 31, 2007.

Correspondence should be addressed to Dr. Fengyi Liang, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. Email: antlfy{at}nus.edu.sg

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				H. B. Werner, K. Kuhlmann, S. Shen, M. Uecker, A. Schardt, K. Dimova, F. Orfaniotou, A. Dhaunchak, B. G. Brinkmann, W. Mobius, et al. Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin J. Neurosci., July 18, 2007; 27(29): 7717 - 7730. [Abstract] [Full Text] [PDF]

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