The Actomyosin Network and Cellular Motility: A S100A4 Regulatory View into the Process

Abstract

Cell migration is a fundamental process responsible for numerous physiological and physiopathological conditions such as inflammation, embryogenesis and cancer. This central aspect of cell biology has seen quantum leaps in our understanding of the coordinated regulations, both spatial and temporal of numerous cytoskeletal proteins and their orchestrations. At the molecular level, this dynamic cellular process can be naively summarised as an engineered cycle composed of three distinct phases of (1) formation of cellular protrusion to initiate contact followed by (2) the adhesion with the external environment/cell-extracellular established connection and (3) the actomyosin force generation to consequently remodel the cytoskeleton. A prominent factor that regulates cellular motility is S100A4, a protein that has received constant attention for its significant role in cellular migration. Consequently, and in order to focus further the impact of this work, the present chapter aims to review some of the actomyosin proteins/complexes that have been demonstrated to be crucial players of the cyclic migration process but are also S100A4 interactors. In doing so, this chapter aims to capture a picture of how expression of this small, calcium-binding protein may, in essence, remodel at different levels the actin organisation and fulfil the motility engineered cycle of protrusion, attachments and contractions.Other than these physiological conditions, cellular motility is essential in regulating some of the physiopathological steps seen in disease. As example, it is well-documented that cellular migration is one of the prominent factors involved in the later stages of carcinogenesis and the subsequent phases of metastasis [9][10][11]. Cancer cell dissemination is clearly dependent upon the ability of migratory tumour cells to evade away from their initial niche, leading to the colonisation and formation of distant secondary lesions in the body [12].At the molecular level, cell migration requires the coordinated regulations, both spatial and temporal of numerous cytoskeletal proteins, to orchestrate the dynamic cellular processes needed for cells to acquire movement. In this context, the actin cytoskeleton and the closely linked myosin network play essential functions [13,14]. The process of cellular motility can be summarised as an engineered cycle composed of three distinct phases which are, (1) formation of cellular protrusion in the forms of lammelipodia and fillopodia to initiate contact and adhesion with the external environment, (2) regulation of cell-extracellular matrix established connections, usually integrin-dependent, and (3) force generation by the actomyosin network which will control both the structure and organisation of the motile architecture [15]. I provide here a brief overview of some of the different elements and protein complexes that are regulated during this migratory cycle, focusing primarily on specific components of the actomyosin complexes.A group of low-molecular weight polypeptides that has been...