Regulation of Actin Assembly Associated With Protrusion and Adhesion in Cell Migration

Abstract

To migrate, a cell first extends protrusions such as lamellipodia and filopodia, forms adhesions, and finally retracts its tail. The actin cytoskeleton plays a major role in this process. The first part of this review (sect. II) describes the formation of the lamellipodial and filopodial actin networks. In lamellipodia, the WASP-Arp2/3 pathways generate a branched filament array. This polarized dendritic actin array is maintained in rapid treadmilling by the concerted action of ADF, profilin, and capping proteins. In filopodia, formins catalyze the processive assembly of nonbranched actin filaments. Cell matrix adhesions mechanically couple actin filaments to the substrate to convert the treadmilling into protrusion and the actomyosin contraction into traction of the cell body and retraction of the tail. The second part of this review (sect. III) focuses on the function and the regulation of major proteins (vinculin, talin, tensin, and alpha-actinin) that control the nucleation, the binding, and the barbed-end growth of actin filaments in adhesions.

Mechanisms of Cell Motion in Confined Geometries

“…At the back of the cell, the cell body contracts and breaks the adhesion points. The resulting overall cell velocity is then limited by the actin polymerisation rate (which however varies substantially between cell types), in agreement with available experimental data [5,27,30].…”

“…Other proteins regulate the nucleation and polymerisation of actin filaments. It is commonly observed that actin polymerisation activators such as WASP proteins preferentially locate along the cell membrane [1,5]. In the case of dendritic cells, actin filaments appear to anchor perpendicularly to the cell membrane, forming structures called podosomes where polymerisation takes place [4].…”

EMT, the cytoskeleton, and cancer cell invasion

“…Here, actin assembly and lateral branching (dendritic nucleation) are mainly controlled by the Arp2/3 complex, a seven subunit protein and major initiator of actin assembly. The activity of the Arp2/3 complex itself is controlled by actin nucleation-promoting factors, such as the N-WASP or the Scar/WAVE complexes which are themselves recruited to and activated at the membrane by Rac1 [172][173][174]. Increased expression of Arp2/3 and WAVE2 has been shown to correlate with poor prognosis in breast and liver carcinomas underlining the relevance of lamellipodia-like structures in cancer progression [175,176].…”

“…Interestingly, metastatic cells are rich in filopodia-like structures, which correlates with their invasiveness [180,181]. Filopodia formation is based on nonbranched, processive actin assembly, controlled by fascin, diaphanous and Ena/VASP [173,182] (Fig. 3 b).…”

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study

“…Therefore, spermatozoa ability to fertilize is tightly associated to a remodeling in cytoskeletal compounds. It is well-known that inositols are involved in cytoskeletal reorganization and in cellular migration (Le Clainche & Carlier, 2008;Windhorst et al, 2008;Johnson & Schell, 2009), and it is likely that MI could ameliorate the fertility rate of the patients with idiopathic infertility acting both on spermatozoa cytoskeleton rearrangements and on their migratory ability.…”