在大腦皮層發(fā)育過程中,，神經(jīng)前體細(xì)胞會不斷的增殖,，新生的神經(jīng)元要不斷遷移以適應(yīng)大腦皮層發(fā)育的需要。皮層神經(jīng)元遷移對于皮層結(jié)構(gòu)和神經(jīng)環(huán)路的形成至關(guān)重要,。已有研究表明細(xì)胞骨架微管對于皮層神經(jīng)元的遷移至關(guān)重要,。微管的性質(zhì)和功能可以受到其組成蛋白α-tubulin和β-tubulin翻譯后修飾的調(diào)節(jié)，其中第40位賴氨酸上乙?；揎椀?alpha;-tubulin在神經(jīng)系統(tǒng)高度富集,，被公認(rèn)為是穩(wěn)定性微管的標(biāo)志，參與調(diào)節(jié)微管與動力蛋白的結(jié)合,。但是α-tubulin乙?；揎椩谏窠?jīng)發(fā)育過程中的作用還不清楚。
9月13日,，《神經(jīng)科學(xué)雜志》發(fā)表了中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所鮑嵐研究組的研究工作：發(fā)現(xiàn)α-tubulin的主要乙?；D(zhuǎn)移酶MEC-17在大腦皮層發(fā)育過程中高表達。通過在體干擾MEC-17的表達可以顯著抑制皮層投射神經(jīng)元的遷移,，在抑制性中間神經(jīng)元發(fā)生區(qū)MGE的體外培養(yǎng)組織中干擾MEC-17表達同樣可以抑制中間神經(jīng)元的遷移,。MEC-17水平降低會阻礙皮層神經(jīng)元在遷移過程中從多極向雙極的轉(zhuǎn)換。進一步的研究表明,，干擾MEC-17可以顯著降低皮層神經(jīng)元α-tubulin第40位賴氨酸上的乙?；剑ㄟ^降低α-tubulin去乙?；窰DAC6或者過表達模擬乙?；?alpha;-tubulinK40Q突變體可以顯著恢復(fù)MEC-17水平降低引起的皮層神經(jīng)元遷移和轉(zhuǎn)換異常。該研究揭示了MEC-17和α-tubulin的乙?；诖竽X皮層發(fā)育過程中的重要作用,，闡述了微管蛋白α-tubulin通過翻譯后修飾影響大腦皮層發(fā)育的細(xì)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(dǎo)下完成,。
該工作得到了中國科學(xué)院,、國家自然科學(xué)基金,、科技部蛋白質(zhì)重大研究計劃等項目的資助。（生物谷Bioon.com）
doi: 10.1523/JNEUROSCI.0016-12.2012
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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.
