[PMID]: | 21948283 |
[Au] Autor: | Zhu H; Zhao L; Wang E; Dimova N; Liu G; Feng Y; Cambi F |
[Ad] Endereço: | Department of Neurology, University of Kentucky, Lexington, Kentucky, USA. |
[Ti] Título: | The QKI-PLP pathway controls SIRT2 abundance in CNS myelin. |
[So] Source: | Glia;60(1):69-82, 2012 Jan. |
[Is] ISSN: | 1098-1136 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Sirtuin 2 (SIRT2), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase expressed by oligodendrocytes (OLs), the myelin-producing cells of the central nervous system (CNS), is markedly up-regulated during active myelination (Li et al. (2007) J Neurosci 27:2606-2616; Southwood et al. (2007) Neurochem Res 32:187-195; Werner et al. (2007) J Neurosci 27:7717-7730). SIRT2 is a component of the myelin proteome and is severely reduced in the Plp1 knockout mouse brain, in which both proteolipid protein (PLP) and DM20 are absent (Werner et al. (2007) J Neurosci 27:7717-7730). The mechanisms that regulate SIRT2 expression in OLs and myelin remain to be investigated. We report for the first time that the expression of SIRT2 is regulated by the QKI-dependent pathway and this effect is mediated through selective regulation of PLP. In the homozygous quakingviable (qk(v) /qk(v) ) mutant mouse that harbors QKI deficiency in OLs (Bockbrader and Feng (2008) Future Neurol 3:655-668; Ebersole et al. (1996) Nat Genet 12:260-265; Hardy et al. (1996) J Neurosci 16:7941-7949), PLP, but not DM20 mRNA, was selectively down-regulated and SIRT2 protein was severely reduced whereas SIRT2 mRNA expression was unaffected. Expression of the cytoplasmic isoform QKI6 in OLs (Zhao et al. (2006) J Neurosci 26:11278-11286) rescued SIRT2 expression in the qk(v) /qk(v) mutant concomitantly with restoration of PLP expression. Moreover, SIRT2 protein is diminished in myelin tracts and compact myelin of the PLP-ISEdel mutant brain, in which PLP protein but not DM20 is selectively reduced (Wang et al. (2008) Exp Neurol 214:322-330). In contrast, SIRT2 expression and its cellular function in regulating process complexity are not affected by the absence of PLP in PLP-ISEdel non-myelinating OLs. Collectively, our results indicate that the abundance of SIRT2 in myelin is dependent on PLP, but not DM20. |
[Mh] Termos MeSH primário: |
Encéfalo/citologia Proteína Proteolipídica de Mielina/metabolismo Bainha de Mielina/metabolismo Oligodendroglia/metabolismo Proteínas de Ligação a RNA/metabolismo Transdução de Sinais/fisiologia Sirtuína 2/metabolismo
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[Mh] Termos MeSH secundário: |
Fatores Etários Animais Animais Recém-Nascidos Diferenciação Celular Citometria de Fluxo Regulação da Expressão Gênica no Desenvolvimento Proteínas de Fluorescência Verde Camundongos Camundongos Endogâmicos C57BL Camundongos Quaking Camundongos Transgênicos Mutação Proteína Proteolipídica de Mielina/genética RNA Mensageiro Proteínas de Ligação a RNA/genética Receptores do Fator Natriurético Atrial/genética Transdução de Sinais/genética Sirtuína 2/genética
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Myelin Proteolipid Protein); 0 (Plp1 protein, mouse); 0 (Qk protein, mouse); 0 (RNA, Messenger); 0 (RNA-Binding Proteins); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 3.5.1.- (Sirt2 protein, mouse); EC 3.5.1.- (Sirtuin 2); EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor); EC 4.6.1.2 (atrial natriuretic factor receptor C) |
[Em] Mês de entrada: | 1203 |
[Cu] Atualização por classe: | 170220 |
[Lr] Data última revisão:
| 170220 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 110928 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1002/glia.21248 |
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