title: The tubulin deacetylase sirtuin-2 regulates neuronal differentiation through the ERK/CREB signaling pathway.
abstract: Modification of microtubule (MT) dynamics is important for diverse aspects of cellular function including differentiation, cargo trafficking, migration, and adhesion. MTs also play a crucial role in the progression of neuronal development. The MT deacetylase Sirtuin 2 (Sirt2) and histone deacetylase 6 (HDAC6) regulate MT dynamics by deacetylating alpha-tubulin (α-tubulin). In this study, we investigated the role of MT deacetylation in the progression of neuronal differentiation. For this, we examined acetylated α-tubulin levels during the differentiation of stem cells into neurons. Acetylated α-tubulin levels were significantly altered during differentiation, and these changes were abolished following treatment with 10 μM AGK2 (Sirt2 inhibitor) or 3 μM tubastatin A (HDAC6 inhibitor). However, neural-specific protein expression (Nestin, NF-M, and MAP-2) was reduced in AGK2-treated hBM-MSCs (AGK-MSCs), but not in tubastatin A-treated hBM-MSCs (Tubastatin A-MSCs). Inhibition of Sirt2 led to a decrease in ERK phosphorylation (p-ERK) level, but HDAC6 inhibition had no such effect. Similar results were obtained for CREB phosphorylation (p-CREB). The results suggest that Sirt2 plays a crucial role in neuronal differentiation via the ERK-CREB signaling pathway.
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, South Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, South Korea.
authors.forename: Sin-Gu
authors.initials: SG
authors.lastname: Jeong
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, South Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, South Korea. Electronic address: gwcho@chosun.ac.kr.
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D056565:Sirtuin 2 / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin; C474199:SIRT2 protein, human; D056565:Sirtuin 2
keywords: Alpha-tubulin; CREB; ERK; Histone deacetylase 6; Mesenchymal stem cells; Sirtuin 2