LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-type lamins.
LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-type lamins.
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DOI：
10.4161/nucl.1.5.12830
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Young SG
中科院分区：
文献类型：
--
作者：
Coffinier C;Fong LG;Young SG
核层蛋白是核层的主要组成部分，在支持细胞核和组织核结构方面起着至关重要的作用。虽然大量临床重要突变已被定位到人类的LMNA基因，但很少有突变与b型纤层蛋白相关。我们已经证明，小白鼠的纤层蛋白b2缺乏会导致严重的脑部异常。虽然lamin b2缺陷小鼠的前脑发育早期阶段似乎是正常的，但皮层神经元无法在大脑皮层内迁移和组织成适当的层。海马和小脑的形态发生也严重受损。这些表型让人联想到无脑畸形，一种以异常神经元迁移为特征的人类大脑发育障碍。无脑畸形患者的大多数突变影响核易位的细胞质调节因子，而核易位是神经元迁移的关键步骤。lamin B2缺陷小鼠的表型表明，lamin B2也可能在核易位中起关键作用。层粘连蛋白B2参与的潜在机制，包括机械和非机械作用，以及参与核膜中的LINC复合物，并讨论了层粘连蛋白B1和B2发挥独特的细胞特异性功能的证据。
Nuclear lamins are major components of the nuclear lamina, and play essential roles in supporting the nucleus and organizing nuclear structures. While a large number of clinically important mutations have been mapped to the LMNA gene in humans, very few mutations have been associated with the B-type lamins. We have shown that lamin B2–deficiency in mice results in severe brain abnormalities. While the early stages of forebrain development in lamin B2–deficient mice appear to be normal, cortical neurons fail to migrate and organize into proper layers within the cerebral cortex. The morphogenesis of the hippocampus and cerebellum is also severely impaired. These phenotypes are reminiscent of lissencephaly, a human brain developmental disorder characterized by an abnormal neuronal migration. Most mutations in lissencephaly patients affect cytoplasmic regulators of nuclear translocation, which is a crucial step in neuronal migration. The phenotypes of lamin B2–deficient mice suggest that lamin B2 may also play a key role in nuclear translocation. Potential mechanisms for lamin B2 involvement, which include mechanical and non-mechanical roles, and participation in LINC complexes in the nuclear envelope, are discussed along with evidence that lamins B1 and B2 play distinct, cell-specific functions.