Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin.
Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin.
复制标题
Nesprin-3是一种新型的外核膜蛋白，与细胞骨架接头蛋白蛋白质相关。
DOI：
10.1083/jcb.200506083
复制
发表时间：
2005-12-05
影响因子：
7.8
通讯作者：
Sonnenberg, Arnoud
中科院分区：
文献类型：
--
作者：
Wilhelmsen, Kevin;Litjens, Sandy H M;Kuikman, Ingrid;Tshimbalanga, Ntambua;Janssen, Hans;van den Bout, Iman;Raymond, Karine;Sonnenberg, Arnoud
尽管它们在细胞生物学中很重要，但维持细胞核在细胞中正确位置的机制还没有很好地理解。这主要是由于对外核膜（ONM）中能够与不同细胞骨架系统相关联的蛋白质的不完全了解。已知两种相关的ONM蛋白，核膜血影蛋白重复序列（nesprin）-1和-2，通过其NH 2末端肌动蛋白结合结构域（ABD）与肌动蛋白细胞骨架直接连接。我们现在已经分离出了nesprin家族的第三个成员，该成员缺乏ABD，而是结合到plakin家族成员plectin，其可以与中间丝（IF）系统相关联。nesprin-3的过表达导致大量的细胞核周边的细胞质凝集素的募集，这是这两种分子与角蛋白-6和-14共定位的地方。重要的是，在角质形成细胞中，网蛋白在细胞表面与整联蛋白α6β4结合，并在ONM与nesprin-3结合，表明细胞核和细胞外基质之间通过IF细胞骨架存在连续连接。
Despite their importance in cell biology, the mechanisms that maintain the nucleus in its proper position in the cell are not well understood. This is primarily the result of an incomplete knowledge of the proteins in the outer nuclear membrane (ONM) that are able to associate with the different cytoskeletal systems. Two related ONM proteins, nuclear envelope spectrin repeat (nesprin)–1 and –2, are known to make direct connections with the actin cytoskeleton through their NH2-terminal actin-binding domain (ABD). We have now isolated a third member of the nesprin family that lacks an ABD and instead binds to the plakin family member plectin, which can associate with the intermediate filament (IF) system. Overexpression of nesprin-3 results in a dramatic recruitment of plectin to the nuclear perimeter, which is where these two molecules are colocalized with both keratin-6 and -14. Importantly, plectin binds to the integrin α6β4 at the cell surface and to nesprin-3 at the ONM in keratinocytes, suggesting that there is a continuous connection between the nucleus and the extracellular matrix through the IF cytoskeleton.