通过与膜相关的酸酶CASK/LIN-2进行核转位和转录调节
Y P Hsueh1, T F Wang, F C Yang
1Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Nature
|April 5, 2000
概括
像CASK这样的膜相关 guanylate kinases (MAGUKs),通常在细胞结点,可以进入细胞核. CASK作为Tbr-1转录因子的联合激活剂,调节对大脑发育至关重要的基因.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 膜相关酸酶 (MAGUKs) 是参与组织细胞信号复合体的支架蛋白.
- 一种MAGUK的CASK/LIN-2对表皮生长因子受体 (EGFR) 的定位和信号传递在*Caenorhabditis elegans*中至关重要.
- 在成年大鼠大脑中,CASK局部化到神经元突触,并与神经素和突触蛋白等突触蛋白相互作用.
研究的目的:
- 调查CASK在细胞结处已知的作用之外的新功能.
- 探索CASK与涉及大脑发育的转录因子之间的相互作用.
- 阐明CASK影响基因转录的机制.
主要方法:
- 同免疫沉测试以确定CASK相互作用的蛋白质.
- 免疫光显微镜以确定神经元内的CASK定位.
- 电泳运动转移试验 (EMSAs) 来评估DNA结合活性.
- 记者基因测定用于测量转录激活.
主要成果:
- CASK通过其酸酶域与T盒转录因子Tbr-1相互作用.
- CASK转移到核中,并与Tbr-1复合在一起,与特定的DNA序列 (T元素) 结合.
- CASK作为Tbr-1的协活性剂起作用,诱导含T元素的基因的转录,包括reelin.
- 里林对于正确的大脑皮层发育至关重要.
结论:
- 马古克在调节基因转录方面具有以前未知的作用.
- 作为Tbr-1的联合激活剂,CASK的核功能对前脑和大脑皮层发育至关重要.
- 这项研究扩展了MAGUK蛋白的已知功能,将细胞结组织与转录控制联系起来.
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