Building distinct actin filament networks in a common cytoplasm

Abstract

Eukaryotic cells generate a diversity of actin filament networks in a common cytoplasm to optimally perform functions such as cell motility, cell adhesion, endocytosis and cytokinesis. Each of these networks maintains precise mechanical and dynamic properties by autonomously controlling the composition of its interacting proteins and spatial organization of its actin filaments. In this review, we discuss the chemical and physical mechanisms that target distinct sets of actin-binding proteins to distinct actin filament populations after nucleation, resulting in the assembly of actin filament networks that are optimized for specific functions.

Figure 1. Actin-based structures and their key conserved regulators in metazoan and yeast cells

(A) Schematic representation of actin-based structures in metazoan (left) and yeast (right) cells. Only a subset of actin-based structures in metazoan cells is presented. The color code distinguishes between branched (Arp2/3-derived) networks (in red) from linear (formin-derived) arrays of actin filaments (in blue and in green). (B) Comparison of the composition of actin-associated proteins in distinct cytoskeletal systems. For metazoan cells (left), red, blue and green circles contain proteins associated with the lamellipodium and/or clathrin–actin endocytic sites, the filopodium and the lamellum, respectively. For yeast cells (right), red, blue and green circles contain proteins associated with clathrin–actin endocytic sites, the cables and the contractile ring, respectively.

Figure 2. Examples of multiple conformations that can be adopted by actin filaments

This image represents three-dimensional reconstructions of six structural modes observed by electron cryomicroscopy of frozen-hydrated actin filaments. T-mode represents a tilted state of the subunits within the filament (modified from [74]).

Figure 3. Model for the formation of Arp2/3-nucleated (branched) and formin-nucleated (linear) networks of actin filaments of distinct protein composition in eukaryotic cells

In this model, actin filaments nucleated by formins (right) and the Apr2/3 complex (left) are generated with distinct conformations, therefore acquiring specific identities at birth (represented by the different colors of the filaments). Tropomyosin specifically decorates formin-nucleated actin filaments and maintains their identity all along their lengths. Arp2/3- and formin/tropomyosin-derived networks subsequently become accessible to specific subsets of ABPs.