Myosin II motor proteins with different functions determine the fate of lamellipodia extension during cell spreading.
Myosin II motor proteins with different functions determine the fate of lamellipodia extension during cell spreading.
复制标题
DOI：
10.1371/journal.pone.0008560
复制
发表时间：
2010-01-05
期刊：
影响因子：
3.7
通讯作者：
Betapudi V
中科院分区：
文献类型：
--
作者：
Betapudi V
非肌细胞表达多种肌球蛋白-II马达蛋白肌球蛋白IIA、肌球蛋白IIB和肌球蛋白IIC，这些肌球蛋白从人类基因组中的不同位点转录。由于它们的序列具有显著的同源性，这些普遍表达的肌球蛋白II马达蛋白被认为具有重叠的细胞功能，但机制细节尚未阐明。本研究揭示了一种机制，协调明显本地化的肌球蛋白IIA和肌球蛋白IIB与意想不到的相反的机械作用，在操纵板状伪足的延伸，在启动细胞入侵，扩散和迁移的关键步骤。肌球蛋白IIB马达蛋白通过定位在前端驱动细胞伸展期间的板状伪足延伸。另一方面，肌球蛋白IIA定位于肌球蛋白IIB旁边，并减弱或收缩板状伪足延伸。肌球蛋白IIA和IIB分别通过调节伸展细胞伸展边缘和中央部分的局灶性接触形成来增加细胞粘附。伸展细胞表达肌球蛋白IIA和肌球蛋白IIB马达蛋白显示一个有组织的肌动蛋白网络组成的逆行丝，弧和中央丝连接到焦点接触。这种有组织的肌动蛋白网络，尤其是伸展边缘的弧和焦点接触形成在肌球蛋白II细胞中丢失。令人惊讶的是，肌球蛋白IIB细胞显示长的平行肌动蛋白丝连接到扩展边缘的焦点接触。因此，在肌动蛋白网络和焦点接触形成的调节中具有不同的作用，肌球蛋白IIA和IIB决定了细胞扩展过程中板状伪足延伸的命运。
Non-muscle cells express multiple myosin-II motor proteins myosin IIA, myosin IIB and myosin IIC transcribed from different loci in the human genome. Due to a significant homology in their sequences, these ubiquitously expressed myosin II motor proteins are believed to have overlapping cellular functions, but the mechanistic details are not elucidated. The present study uncovered a mechanism that coordinates the distinctly localized myosin IIA and myosin IIB with unexpected opposite mechanical roles in maneuvering lamellipodia extension, a critical step in the initiation of cell invasion, spreading, and migration. Myosin IIB motor protein by localizing at the front drives lamellipodia extension during cell spreading. On the other hand, myosin IIA localizes next to myosin IIB and attenuates or retracts lamellipodia extension. Myosin IIA and IIB increase cell adhesion by regulating focal contacts formation in the spreading margins and central part of the spreading cell, respectively. Spreading cells expressing both myosin IIA and myosin IIB motor proteins display an organized actin network consisting of retrograde filaments, arcs and central filaments attached to focal contacts. This organized actin network especially arcs and focal contacts formation in the spreading margins were lost in myosin IIÂ cells. Surprisingly, myosin IIB̂ cells displayed long parallel actin filaments connected to focal contacts in the spreading margins. Thus, with different roles in the regulation of the actin network and focal contacts formation, both myosin IIA and IIB determine the fate of lamellipodia extension during cell spreading.
登录
查看更多内容
影响因子：
56.9
作者：
Hu, Ke;Ji, Lin;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
影响因子：
3.3
作者：
Breckenridge, Mark T.;Dulyaninova, Natalya G.;Egelhoff, Thomas T.
通讯作者：
Egelhoff, Thomas T.
影响因子：
4
作者：
Brown, ME;Bridgman, PC
通讯作者：
Bridgman, PC
影响因子：
2.1
作者：
Amano, M;Chihara, K;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
3.5
作者：
Leal, A;Endele, S;Rautenstrauss, B
通讯作者：
Rautenstrauss, B