在大腦皮層發育過程中，神經前體細胞會不斷的增殖，新生的神經元要不斷遷移以適應大腦皮層發育的需要。皮層神經元遷移對於皮層結構和神經環路的形成至關重要。已有研究表明細胞骨架微管對於皮層神經元的遷移至關重要。微管的性質和功能可以受到其組成蛋白α-tubulin和β-tubulin翻譯後修飾的調節，其中第40位賴氨酸上乙醯化修飾的α-tubulin在神經系統高度富集，被公認為是穩定性微管的標誌，參與調節微管與動力蛋白的結合。但是α-tubulin乙醯化修飾在神經發育過程中的作用還不清楚。
9月13日，《神經科學雜誌》發表了中國科學院上海生命科學研究院生物化學與細胞生物學研究所鮑嵐研究組的研究工作：發現α-tubulin的主要乙醯基轉移酶MEC-17在大腦皮層發育過程中高表達。通過在體幹擾MEC-17的表達可以顯著抑制皮層投射神經元的遷移，在抑制性中間神經元發生區MGE的體外培養組織中幹擾MEC-17表達同樣可以抑制中間神經元的遷移。MEC-17水平降低會阻礙皮層神經元在遷移過程中從多極向雙極的轉換。進一步的研究表明，幹擾MEC-17可以顯著降低皮層神經元α-tubulin第40位賴氨酸上的乙醯化水平，通過降低α-tubulin去乙醯化酶HDAC6或者過表達模擬乙醯化的α-tubulinK40Q突變體可以顯著恢復MEC-17水平降低引起的皮層神經元遷移和轉換異常。該研究揭示了MEC-17和α-tubulin的乙醯化在大腦皮層發育過程中的重要作用，闡述了微管蛋白α-tubulin通過翻譯後修飾影響大腦皮層發育的細胞機制。該項工作由博士研究生李磊等在鮑嵐研究員的指導下完成。
該工作得到了中國科學院、國家自然科學基金、科技部蛋白質重大研究計劃等項目的資助。（生物谷Bioon.com）
MEC-17 Deficiency Leads to Reduced α-Tubulin Acetylation and Impaired Migration of Cortical Neurons
Lei Li, Dan Wei, Qiong Wang, Jing Pan, Rong Liu, Xu Zhang, and Lan Bao
Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics can be modulated by posttranslational modifications to tubulin subunits. Acetylation of α-tubulin at lysine 40 is important in regulating microtubule properties, and this process is controlled by acetyltransferase and deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has been found to play a major role in the acetylation of α-tubulin in different species in vivo. However, the physiological function of MEC-17 during neural development is largely unknown. Here, we report that MEC-17 is critical for the migration of cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex during development. MEC-17 deficiency caused migratory defects in the cortical projection neurons and interneurons, and perturbed the transition of projection neurons from the multipolar stage to the unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulinK40Q to mimic acetylated α-tubulin could reduce the migratory and morphological defects caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which regulates the acetylation of α-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and α-tubulin acetylation in cortical development.