A very different, well-studied web-forming protein is spectrin, which was first identified in red blood cells. Spectrin is a long, flexible protein made out of four elongated polypeptide chains (two α subunits and two β subunits), arranged so that the two actin-filament-binding sites are about 200 nm apart (compared with 14 nm for fimbrin and about 30 nm for α-actinin; see Figure 16–23). In the red blood cell, spectrin is concentrated just beneath the plasma membrane, where it forms a two-dimensional weblike network held together by short actin filaments whose precise lengths are tightly regulated by capping proteins at each end; spectrin links this web to the plasma membrane because it has separate binding sites for peripheral membrane proteins, which are themselves positioned near the lipid bilayer by integral membrane proteins (see Figure 10–38). The resulting network creates a strong, yet flexible cell cortex that provides mechanical support for the overlying plasma membrane, allowing the red blood cell to spring back to its original shape after squeezing through a capillary. Close relatives of spectrin are found in the cortex of most other vertebrate cell types, where they also help to shape and stiffen the surface membrane. A particularly striking example of spectrin’s role
Figure 16–23 The formation of two types of actin filament bundles.
(A) Fimbrin cross-links actin filaments into tight bundles, which exclude the motor protein myosin II from participating in the assembly. In contrast, α-actinin, which is a homodimer, cross-links actin filaments into loose bundles, which allow myosin (not shown) to incorporate into the bundle. Fimbrin and α-actinin tend to exclude one another because of the very different spacing of the actin filament bundles that they form. (B) Electron micrograph of purified α-actinin molecules. (B, courtesy of John Heuser.) in promoting mechanical stability is the long, thin axon of neurons in the nematode worm Caenorhabditis elegans, where spectrin is required to keep them from breaking during the twisting motions the worms make during crawling.
The connections of the cortical actin cytoskeleton to the plasma membrane are only partially understood. Members of the ERM family (named for its first three members, ezrin, radixin, and moesin), help organize membrane domains through their ability to interact with transmembrane proteins and the underlying cytoskeleton. In so doing, they not only provide structural links to strengthen the cell cortex, but also regulate the activities of signal transduction pathways. Moesin also increases cortical stiffness to promote cell rounding during mitosis. Measurements by atomic force microscopy indicate that the cell cortex remains soft during mitosis when moesin is depleted. ERM proteins are thought to bind to and organize the cortical actin cytoskeleton in a variety of contexts, thereby affecting the shape and stiffness of the membrane as well as the localization and activity of signaling molecules.
Bacteria Can Hijack the Host Actin Cytoskeleton
The importance of accessory proteins in actin-based motility and force production is illustrated beautifully by studies of certain bacteria and viruses that use components of the host-cell actin cytoskeleton to move through the cytoplasm. The cytoplasm of mammalian cells is extremely viscous, containing organelles and cytoskeletal elements that inhibit diffusion of large particles like bacteria or viruses. To move around in a cell and invade neighboring cells, several pathogens, including Listeria monocytogenes (which causes a rare but serious form of food poisoning), overcome this problem by recruiting and activating the Arp 2/3 complex at their surface. The Arp 2/3 complex nucleates the assembly of actin filaments that generate a substantial force and push the bacterium through the