TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton.
TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton.
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DOI：
10.1242/jcs.029454
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发表时间：
2008-10-15
影响因子：
4
通讯作者：
Breakefield XO
中科院分区：
文献类型：
--
作者：
Nery FC;Zeng J;Niland BP;Hewett J;Farley J;Irimia D;Li Y;Wiche G;Sonnenberg A;Breakefield XO
torsinA 的特定突变 (ΔE) 是大多数显性遗传性运动障碍、早发性扭转肌张力障碍 (DYT1) 病例的基础。 TorsinA 是 AAA+ ATP 酶超家族的成员，位于核膜 (NE) 和内质网 (ER) 的管腔内。我们研究了 torsinA 和 nesprin-3 之间的关联，它跨越 NE 的外核膜 (ONM)，并通过成纤维细胞中的凝集素将其与波形蛋白连接。小鼠 nesprin-3α 与 torsinA 共免疫沉淀，涉及 torsinA 的 C 末端区域和 nesprin-3α 的 KASH 结构域。 torsinAΔE 与人 nesprin-3 的这种关联似乎比 torsinA 更强。 TorsinA 还与 nesprin-1 和 -2（SYNE1 和 2）的 KASH 结构域相关，后者与肌动蛋白相连。在缺少torsinA的情况下，在敲除小鼠胚胎成纤维细胞（MEF）中，nesprin-3主要定位于内质网。在 DYT1 患者的成纤维细胞中也观察到 ER 中黄色荧光蛋白 (YFP)-nesprin-3 的富集，形成富含 torsinA、波形蛋白和肌动蛋白的 YFP 阳性球状结构。 TorsinA 缺失的 MEF 具有正常的 NE 结构，但与野生型 MEF 相比，在伤口愈合测定中核极化和细胞迁移被延迟。这些研究支持 torsinA 在 NE 腔中 nesprins 的 KASH 结构域与其蛋白伴侣之间动态相互作用中的作用，torsinA 影响 nesprins 和相关细胞骨架元件的定位，并影响它们在核和细胞运动中的作用。
A specific mutation (ΔE) in torsinA underlies most cases of the dominantly inherited movement disorder, early-onset torsion dystonia (DYT1). TorsinA, a member of the AAA+ ATPase superfamily, is located within the lumen of the nuclear envelope (NE) and endoplasmic reticulum (ER). We investigated an association between torsinA and nesprin-3, which spans the outer nuclear membrane (ONM) of the NE and links it to vimentin via plectin in fibroblasts. Mouse nesprin-3α co-immunoprecipitated with torsinA and this involved the C-terminal region of torsinA and the KASH domain of nesprin-3α. This association with human nesprin-3 appeared to be stronger for torsinAΔE than for torsinA. TorsinA also associated with the KASH domains of nesprin-1 and -2 (SYNE1 and 2), which link to actin. In the absence of torsinA, in knockout mouse embryonic fibroblasts (MEFs), nesprin-3 was localized predominantly in the ER. Enrichment of yellow fluorescent protein (YFP)-nesprin-3 in the ER was also seen in the fibroblasts of DYT1 patients, with formation of YFP-positive globular structures enriched in torsinA, vimentin and actin. TorsinA-null MEFs had normal NE structure, but nuclear polarization and cell migration were delayed in a wound-healing assay, as compared with wild-type MEFs. These studies support a role for torsinA in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the NE, with torsinA influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement.
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影响因子：
6.1
作者：
Grundmann, K.;Reischmann, B.;Riess, O.
通讯作者：
Riess, O.
影响因子：
4.8
作者：
Esue, Osigwe;Carson, Ashley A.;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
8.6
作者：
Carbon, Maren;Kingsley, Peter B.;Eidelberg, David
通讯作者：
Eidelberg, David
DOI：
10.2152/jmi.52.272
发表时间：
2005-11-01
期刊：
The journal of medical investigation : JMI
影响因子：
--
作者：
Asanuma, Kotaro;Carbon-Correll, Maren;Eidelberg, David
通讯作者：
Eidelberg, David
影响因子：
7.8
作者：
Crisp, M;Liu, Q;Hodzic, D
通讯作者：
Hodzic, D