Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration
Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration
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DOI：
10.1073/pnas.1303916110
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发表时间：
2013-05-21
影响因子：
11.1
通讯作者：
Young, Stephen G.
中科院分区：
文献类型：
--
作者：
Jung, Hea-Jin;Nobumori, Chika;Young, Stephen G.
蛋白质法尼化在层蛋白A生物发生和早衰症发病机制中的作用已经有了相当详细的研究，但对于B型层蛋白，层蛋白B1和层蛋白B2的重要性却鲜有人关注。从发育的最早阶段起，层蛋白B1和B2在几乎每种类型的细胞中都有表达，它们参与了细胞核内的各种功能。为了评估蛋白质法尼化对B型Lamins的重要性，我们创造了表达非法尼化形式的lamin B1和lamin B2的敲入小鼠。表达非法尼化层蛋白B2的小鼠发育正常，没有疾病。相比之下，表达非法尼化层蛋白B1的小鼠出生后不久就死亡，并伴有严重的神经发育缺陷和显著的神经元核异常。迁移神经元中的核膜被从染色质中拉出，使染色质“裸露”(没有核膜)。因此，层蛋白B1的法尼化--而不是层蛋白B2--对于大脑发育和在神经元迁移过程中将染色质保留在核层边界内是至关重要的。
The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest stages of development, and they have been implicated in a variety of functions within the cell nucleus. To assess the importance of protein farnesylation for B-type lamins, we created knock-in mice expressing nonfarnesylated versions of lamin B1 and lamin B2. Mice expressing nonfarnesylated lamin B2 developed normally and were free of disease. In contrast, mice expressing nonfarnesylated lamin B1 died soon after birth, with severe neurodevelopmental defects and striking nuclear abnormalities in neurons. The nuclear lamina in migrating neurons was pulled away from the chromatin so that the chromatin was left "naked" (free from the nuclear lamina). Thus, farnesylation of lamin B1-but not lamin B2-is crucial for brain development and for retaining chromatin within the bounds of the nuclear lamina during neuronal migration.