Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization.
Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization.
复制标题
层固定杆域中的参与对核组织很重要的异型层粘连相互作用。
DOI：
10.1083/jcb.153.3.479
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发表时间：
2001-04-30
影响因子：
7.8
通讯作者：
Gerace, L
中科院分区：
文献类型：
--
作者：
Schirmer, E C;Guan, T;Gerace, L
核纤层是一种中间型丝蛋白（核纤层蛋白）的网状结构，排列在内核膜上。层被认为是核结构的一个重要决定因素，但这一想法几乎没有直接的检验。为了研究核纤层蛋白的功能，我们发现了一种新的核纤层蛋白B1突变体，该突变体缺失了α-螺旋杆结构域的中间区Δ 4/5。虽然只保留了10个七头的杆，这种突变体组装成中间体的类似结构在体外。当在培养的细胞中表达时，它集中在核膜的斑块中。同时，内源性核纤层从均匀分布转变为斑片状分布，并失去其完整的共定位，核变得高度分叶状。体外结合研究表明，内部杆区域是重要的异型协会的核纤层蛋白B1，这反过来又需要适当的组织的层。伴随着突变体的表达诱导的纤层结构的变化，核孔复合物和内膜簇的整合膜蛋白，主要是在内源性纤层蛋白的补丁。综合考虑，这些数据表明核纤层蛋白在组织核膜中的其他蛋白质和决定核形状方面发挥着重要作用。
The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characterized a novel lamin B1 mutant lacking the middle ∼4/5 of its α-helical rod domain. Though retaining only 10 heptads of the rod, this mutant assembles into intermediate filament-like structures in vitro. When expressed in cultured cells, it concentrates in patches at the nuclear envelope. Concurrently, endogenous lamins shift from a uniform to a patchy distribution and lose their complete colocalization, and nuclei become highly lobulated. In vitro binding studies suggest that the internal rod region is important for heterotypic associations of lamin B1, which in turn are required for proper organization of the lamina. Accompanying the changes in lamina structure induced by expression of the mutant, nuclear pore complexes and integral membrane proteins of the inner membrane cluster, principally at the patches of endogenous lamins. Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape.