Heath J P, Holifield B F
Department of Pediatrics (CNRC), Baylor College of Medicine, Houston, TX 77030.
Symp Soc Exp Biol. 1993;47:35-56.
In this review we discuss the organization of F-actin in motile fibroblasts in relation to the phenomenon of cortical actin flow; we review some of the mechanisms proposed to drive this process and then relate some of our new findings on the interactions of cortical flow and substratum adhesions in fibroblasts. It is our thesis that the centripetal flow of F-actin through the lamellipodium and leading lamella is the major determining factor organising the polarized stress fiber system and associated cell-substratum adhesions in crawling fibroblastic cells. The broad flattened region of cytoplasm anterior to the nucleus, called the leading lamella, is fringed with much thinner structures, the lamellipodia, which are the primary protrusive organelles of motile cells. Lamellipodia are filled with a criss-crossed network of actin filaments interspersed with small bundles or ribs. In the leading lamella, the actin cytoskeleton is largely confined to two cortical layers beneath the dorsal and ventral cell surfaces. The ventral cortex is engaged in cell adhesion; the dorsal cortex is made up of a circumferentially orientated sheet of actin filaments and bundles which we team the dorsal cortical microfilament sheath (DCMS). Stress fibers insert into the ventral adhesions and pass back through the lamella rising up to meet the DCMS. Cortical flow appears to be a constitutive process in most types of cells when they become motile. In fibroblasts a continuous centripetal flux of structure is seen flowing through the lamellipodium and into the more central regions of the lamella at approximately 0.1 micron per second. Some of the structures engaged in the flux pass back and merge into the DCMS which is also moving rearward at a slower rate of 1 to 5 microns per minute. We find that the formation of a stress fibre is a direct consequence of cortical flow. Initially, stress fibre formation involves the establishment of a focal adhesion between an F-actin bundle in the lamellipodium and the substratum. Subsequently, a fibre grows centripetally from the adhesion and elongates coordinately with the rearward flowing cortex. Cortical flow is restrained locally at the distal end of the nascent fibre leading to indentation and folding of the sheet of filaments. This fold develops into an arc. We demonstrate that mechanical linkages exist between the lamellipodium and the DCMS. Cytochalasin induces a sudden and massive centripetal collapse of the DCMS which drags the lamellipodia with it.(ABSTRACT TRUNCATED AT 400 WORDS)
在本综述中，我们讨论了运动性成纤维细胞中F-肌动蛋白的组织与皮质肌动蛋白流现象的关系；我们回顾了一些被认为驱动这一过程的机制，然后阐述了我们关于成纤维细胞中皮质流与基质黏附相互作用的一些新发现。我们的论点是，F-肌动蛋白通过片足和前缘的向心流动是组织爬行的成纤维细胞中极化应力纤维系统及相关细胞-基质黏附的主要决定因素。细胞核前方宽阔扁平的细胞质区域称为前缘，其边缘是薄得多的结构，即片足，片足是运动细胞的主要突出细胞器。片足充满了纵横交错的肌动蛋白丝网络，其间散布着小束或肋状结构。在前缘，肌动蛋白细胞骨架主要局限于细胞背侧和腹侧表面下方的两个皮质层。腹侧皮质参与细胞黏附；背侧皮质由一圈沿圆周方向排列的肌动蛋白丝和束组成，我们将其称为背侧皮质微丝鞘（DCMS）。应力纤维插入腹侧黏附部位，并向后穿过薄片，向上延伸与DCMS会合。当大多数类型的细胞开始运动时，皮质流似乎是一个组成性过程。在成纤维细胞中，可以看到一种持续的向心结构流以每秒约0.1微米的速度流过片足并进入薄片的更中心区域。一些参与流动的结构向后返回并融入DCMS，DCMS也以每分钟1至5微米的较慢速度向后移动。我们发现应力纤维的形成是皮质流的直接结果。最初，应力纤维的形成涉及片足中的F-肌动蛋白束与基质之间形成焦点黏附。随后，纤维从黏附部位向心生长，并与向后流动的皮质协调伸长。皮质流在新生纤维的远端局部受到抑制，导致丝状薄片凹陷和折叠。这个褶皱发展成一个弧形。我们证明片足和DCMS之间存在机械联系。细胞松弛素会导致DCMS突然大量向心塌陷，并随之拉动片足。（摘要截选至400字）
