Comparative Biochemical Analysis Suggests That Vinculin and Metavinculin Cooperate in Muscular Adhesion Sites*
Comparative Biochemical Analysis Suggests That Vinculin and Metavinculin Cooperate in Muscular Adhesion Sites*
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比较生化分析表明纽蛋白和美达纽蛋白在肌肉粘附部位协同作用*
DOI：
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发表时间：
2004
影响因子：
4.8
通讯作者：
S. Illenberger
中科院分区：
文献类型：
--
作者：
S. Witt;A. Zieseniss;U. Fock;B. Jockusch;S. Illenberger
后黏着斑蛋白是细胞粘附蛋白黏着斑蛋白的肌肉特异性剪接变体，其特征在于C-末端尾部结构域内的68个氨基酸插入。该区域内的突变与人类遗传性特发性扩张型心肌病相关的研究结果表明，metavinculin对肌肉肌动蛋白膜附着位点的分子结构有特定的贡献，然而，其性质仍然未知。在小鼠中，后黏着斑蛋白在平滑肌和骨骼肌中表达，在那里它分别与黏着斑蛋白共定位在致密斑块和肋部中，但在心脏中的丰度明显较低。免疫沉淀表明，这两种亚型存在于同一复合物中。在分子水平上，两种黏着斑蛋白同种型均通过分子内头-尾相互作用进行调节，与黏着斑蛋白尾部相比，后黏着斑蛋白尾部结构域对头部具有较低的亲和力。此外，metavinculin显示与酸性磷脂的结合受损和同源二聚化减少。只有在磷脂活化的黏着斑蛋白尾的存在下，后黏着斑蛋白尾结构域才容易掺入异二聚体中。突变分析表明，metavinculin插入显着改变的C-末端发夹环酸性磷脂的结合。总之，我们的数据导致了一种模型，其中68个氨基酸插入物的负电荷损害了后黏着斑蛋白尾部结构域的展开，因此需要黏着斑蛋白完全激活后黏着斑蛋白分子。因此，微丝锚定可以通过异二聚体的形成在肌肉粘连部位进行调节。
Metavinculin, the muscle-specific splice variant of the cell adhesion protein vinculin, is characterized by a 68-amino acid insert within the C-terminal tail domain. The findings that mutations within this region correlate with hereditary idiopathic dilated cardiomyopathy in man suggest a specific contribution of metavinculin to the molecular architecture of muscular actin-membrane attachment sites, the nature of which, however, is still unknown. In mice, metavinculin is expressed in smooth and skeletal muscle, where it co-localizes with vinculin in dense plaques and costameres, respectively, but is of conspicuously low abundance in the heart. Immunoprecipitates suggest that both isoforms are present in the same complex. On the molecular level, both vinculin isoforms are regulated via an intramolecular head-tail interaction, with the metavinculin tail domain having a lower affinity for the head as compared with the vinculin tail. In addition, metavinculin displays impaired binding to acidic phospholipids and reduced homodimerization. Only in the presence of phospholipid-activated vinculin tail, the metavinculin tail domain is readily incorporated into heterodimers. Mutational analysis revealed that the metavinculin insert significantly alters binding of the C-terminal hairpin loop to acidic phospholipids. In summary, our data lead to a model in which unfurling of the metavinculin tail domain is impaired by the negative charges of the 68-amino acid insert, thus requiring vinculin to fully activate the metavinculin molecule. As a consequence, microfilament anchorage may be modulated at muscular adhesion sites through heterodimer formation.
纽蛋白头部和尾部结构域之间的分子内关联调节踝蛋白结合。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Johnson,RP;Craig,SW
通讯作者：
Craig,SW
影响因子：
4.6
作者：
Weiming Xu;H. Baribault;E. Adamson
通讯作者：
Weiming Xu;H. Baribault;E. Adamson
DOI：
10.1073/pnas.92.20.9161
发表时间：
1995-09-26
影响因子：
11.1
作者：
COLL, JL;BENZEEV, A;ADAMSON, ED
通讯作者：
ADAMSON, ED