一种神经干细胞干性维持蛋白——TRIM32（附全文）

wk168

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奥地利研究人员最新研究发现，一种蛋白质在神经发育中起关键作用，从而进一步揭示了神经干细胞分化成神经元的机理，在大脑发育研究方面取得了新的进展。2 v4 P$ _' u1 c& D
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奥地利科学院分子生物技术研究所等机构的研究人员对老鼠大脑皮层的研究显示，一种名为“TRIM32”的蛋白质控制着神经元的形成过程。神经元是高等动物神经系统的结构单位和功能单位，其基本功能是通过接收、整合、传导和输出信息实现信息交换。它由神经干细胞分化而成。- }  m9 A: ]$ o# P! E+ q" h

9 [. w- K$ g0 T, x神经干细胞在分化过程中通常生成两个细胞，一个是神经元，另一个则保持神经干细胞的状态，以反复分化。研究人员发现，“TRIM32”蛋白质的表达能促进神经干细胞生成神经元，如果这种蛋白质的表达被抑制，则两个子细胞都会保持神经干细胞的状态。: X8 H) J9 P! o7 {3 b

4 T" ^3 f8 b, k. k  F; E研究人员克诺布利希介绍说，这项成果在许多方面具有实用价值。如果治疗某种疾病需要神经干细胞，那么可以通过抑制“TRIM32”的表达来培养更多的神经干细胞；如果需要激活成年人大脑中仍在睡眠的神经干细胞，以形成新的神经元，也可以采取促进这种蛋白质表达的方法。! W0 o9 \2 ^0 ~+ N. i. t; B. w1 m

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文章出处：2 r7 K0 z* ]5 P- E+ Y1 Z5 d
Cell,6 March 2009 doi:10.1016/j.cell.2008.12.024
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The TRIM-NHL Protein TRIM32 Activates MicroRNAs and Prevents Self-Renewal in Mouse Neural Progenitors5 B2 |" X  S6 \) M7 o8 V0 ^
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Jens C. Schwamborn1,Eugene Berezikov2andJuergen A. Knoblich1,,( b+ U  v# k- ]: x  w1 j5 G
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Summary
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In the mouse neocortex, neural progenitor cells generate both differentiating neurons and daughter cells that maintain progenitor fate. Here, we show that the TRIM-NHL protein TRIM32 regulates protein degradation and microRNA activity to control the balance between those two daughter cell types. In both horizontally and vertically dividing progenitors, TRIM32 becomes polarized in mitosis and is concentrated in one of the two daughter cells. TRIM32 overexpression induces neuronal differentiation while inhibition of TRIM32 causes both daughter cells to retain progenitor cell fate. TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs. We show that Let-7 is one of the TRIM32 targets and is required and sufficient for neuronal differentiation. TRIM32 is the mouse ortholog of Drosophila Brat and Mei-P26 and might be part of a protein family that regulates the balance between differentiation and proliferation in stem cell lineages.

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