A unique role for nonmuscle myosin heavy chain IIA in regulation of epithelial apical junctions.
A unique role for nonmuscle myosin heavy chain IIA in regulation of epithelial apical junctions.
复制标题
非肌肉肌球蛋白重链IIA在调节上皮顶连接处的独特作用。
DOI：
10.1371/journal.pone.0000658
复制
发表时间：
2007-08-01
期刊：
影响因子：
3.7
通讯作者：
Parkos, Charles A.
中科院分区：
文献类型：
--
作者：
Ivanov, Andrei I.;Bachar, Moshe;Babbin, Brian A.;Adelstein, Robert S.;Nusrat, Asma;Parkos, Charles A.
上皮屏障的完整性和功能依赖于由紧密连接和粘附连接组成的顶端连接复合体（AJC），并受底层肌动蛋白丝的调节。一种主要的f -肌动蛋白马达，肌凝蛋白II，先前被认为与AJC的调节有关，然而，肌凝蛋白II参与AJC动力学的直接证据缺乏，而且调节哺乳动物上皮顶端连接形成和拆卸的肌凝蛋白II马达的分子身份尚不清楚。我们研究了非肌球蛋白II （NMMII）重链异构体A、B和C在上皮AJC动力学和功能调控中的作用。在模型肠上皮细胞系中观察到三种NMMII亚型的表达，所有亚型都聚集在结周f -肌动蛋白带内。sirna介导的下调SK-CO15结肠上皮细胞中NMMIIA的表达，而不下调NMMIIB或NMMIIC的表达，导致细胞形态和细胞间粘附的深刻变化。这些变化包括获得成纤维细胞样细胞形状，细胞旁屏障缺陷，粘附物和紧密连接的组装和拆卸的大量衰减。NMMIIA敲除后，观察到AJC的组装受损，包括周围肌动蛋白丝的剧烈紊乱。这些发现为肌球蛋白ii依赖性调节哺乳动物上皮AJC动力学提供了第一个直接的非药物证据，并强调了NMMIIA在连接生物发生中的独特作用。
The integrity and function of the epithelial barrier is dependent on the apical junctional complex (AJC) composed of tight and adherens junctions and regulated by the underlying actin filaments. A major F-actin motor, myosin II, was previously implicated in regulation of the AJC, however direct evidence of the involvement of myosin II in AJC dynamics are lacking and the molecular identity of the myosin II motor that regulates formation and disassembly of apical junctions in mammalian epithelia is unknown. We investigated the role of nonmuscle myosin II (NMMII) heavy chain isoforms, A, B, and C in regulation of epithelial AJC dynamics and function. Expression of the three NMMII isoforms was observed in model intestinal epithelial cell lines, where all isoforms accumulated within the perijunctional F-actin belt. siRNA-mediated downregulation of NMMIIA, but not NMMIIB or NMMIIC expression in SK-CO15 colonic epithelial cells resulted in profound changes of cell morphology and cell-cell adhesions. These changes included acquisition of a fibroblast-like cell shape, defective paracellular barrier, and substantial attenuation of the assembly and disassembly of both adherens and tight junctions. Impaired assembly of the AJC observed after NMMIIA knock-down involved dramatic disorganization of perijunctional actin filaments. These findings provide the first direct non-pharmacological evidence of myosin II-dependent regulation of AJC dynamics in mammalian epithelia and highlight a unique role of NMMIIA in junctional biogenesis.
登录
查看更多内容
DOI：
10.1083/jcb.107.4.1575
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gumbiner B;Stevenson B;Grimaldi A
通讯作者：
Grimaldi A
影响因子：
--
作者：
Cramer, LP;Briggs, LJ;Dawe, HR
通讯作者：
Dawe, HR
DOI：
10.1152/ajpcell.1996.271.5.c1678
发表时间：
1996-11-01
影响因子：
5.5
作者：
Hecht, G;Pestic, L;deLanerolle, P
通讯作者：
deLanerolle, P
影响因子：
4.8
作者：
Kovács, M;Tóth, J;Sellers, JR
通讯作者：
Sellers, JR
影响因子：
4.8
作者：
Bao, JJ;Jana, SS;Adelstein, RS
通讯作者：
Adelstein, RS