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Cell Rep.:科学家揭示神经干细胞分化新的调控机制

来源:生物谷 2013-10-26 14:09

2013年10月26日讯 /生物谷BIOON/--为什么人类和其他哺乳动物如此的聪明?USC科学家Wange Lu博士在发表于Cell Reports杂志上的文章部分回答了这个问题。

科学家揭示了神经干细胞和前体细胞如何分化成神经元和胶质细胞的机制。神经元通过电信号和化学信号传递信息;胶质细胞环绕并支持和保护神经元。胶质细胞承担了支持神经元的一切活动,如提供养料、氧气,保护神经元免受病原体侵染等。

Lu带领研究团队在培养皿中研究了早期小鼠胚胎的神经干细胞,发现SMEK1蛋白能够促进神经干细胞和前体细胞的分化。同时SMEK1又能抑制这些细胞的异常分裂。

SMEK1蛋白并不是单兵作战,科学家发现该蛋白与蛋白磷酸化酶4相互作用抑制第三类蛋白PAR3的活性。PAR3被抑制后,神经干细胞和前体细胞就能够分化成新生的神经元和胶质细胞。

Wange Lu博士称,该研究揭示了大脑形成时干细胞和神经元的平衡机制。如果该平衡被打破就会导致肿瘤的产生,或其他神经系统疾病。

该研究还为治疗神经退行性疾病提供了重要依据,为治疗AD,PD和现今难治愈的疾病带来了希望。(生物谷Bioon.com)

Protein Phosphatase 4 and Smek Complex Negatively Regulate Par3 and Promote Neuronal Differentiation of Neural Stem/Progenitor Cells

Jungmook Lyu, Hee-Ryang Kim, Vicky Yamamoto, Si Ho Choi, Zong Wei, Choun-Ki Joo, Wange Lu

Neural progenitor cells (NPCs) are multipotent cells that can self-renew and differentiate into neurons and glial cells. However, mechanisms that control their fate decisions are poorly understood. Here, we show that Smek1, a regulatory subunit of the serine/threonine protein phosphatase PP4, promotes neuronal differentiation and suppresses the proliferative capacity of NPCs. We identify the cell polarity protein Par3, a negative regulator of neuronal differentiation, as a Smek1 substrate and demonstrate that Smek1 suppresses its activity. We also show that Smek1, which is predominantly nuclear in NPCs, is excluded from the nucleus during mitosis, allowing it to interact with cortical/cytoplasmic Par3 and mediate its dephosphorylation by the catalytic subunit PP4c. These results identify the PP4/Smek1 complex as a key regulator of neurogenesis.

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