Each type of bundling protein also determines which other molecules can interact with the cross-linked actin filaments. Myosin II is the motor protein that enables stress fibers and other contractile arrays to contract. The very close packing of actin filaments caused by the small monomeric bundling protein fimbrin apparently excludes myosin, and thus the parallel actin filaments held together by fimbrin are not contractile. On the other hand, α-actinin cross-links oppositely
Figure 16–21 Actin arrays in a cell.
A fibroblast crawling in a tissue-culture dish is shown with four areas enlarged to show the arrangement of actin filaments. The actin filaments are shown in red, with arrowheads pointing toward the minus end. Stress fibers are contractile and exert tension. The actin cortex underlies the plasma membrane and consists of gel-like networks or dendritic actin networks that enable membrane protrusion at lamellopodia. Filopodia are spike-like projections of the plasma membrane that allow a cell to explore its environment.
Figure 16–22 The modular structures of four actin-cross-linking proteins. Each of the proteins shown has two actin-binding sites (red) that are related in sequence. Fimbrin has two directly adjacent actinbinding sites, so that it holds its two actin filaments very close together (14 nm apart), aligned with the same polarity (see Figure 16–23A). The two actin-binding sites in α-actinin are separated by a spacer around 30 nm long, so that it forms more loosely packed actin bundles (see Figure 16–23A). Filamin has two actin-binding sites with a V-shaped linkage between them, so that it cross-links actin filaments into a network with the filaments oriented almost at right angles to one another (see Figure 16–24). Spectrin is a tetramer of two α and two β subunits, and the tetramer has two actinbinding sites spaced about 200 nm apart (see Figure 10–38).
polarized actin filaments into loose bundles, allowing the binding of myosin and formation of contractile actin bundles (Figure 16–23). Because of the very different spacing and orientation of the actin filaments, bundling by fimbrin automatically discourages bundling by α-actinin, and vice versa, so that the two types of bundling protein are mutually exclusive.
The bundling proteins that we have discussed so far have straight, stiff connections between their two actin-filament-binding domains. Other actin cross-linking proteins have either a flexible or a stiff, bent connection between their two binding domains, allowing them to form actin filament webs or gels, rather than actin bundles. Filamin (see Figure 16–22) promotes the formation of a loose and highly viscous gel by clamping together two actin filaments roughly at right angles (Figure 16–24A). Cells require the actin gels formed by filamin to extend the thin, sheetlike membrane projections called lamellipodia that help them to crawl across solid surfaces. In humans, mutations in the filamin A gene cause defects in nerve-cell migration during early embryonic development. Cells in the periventricular region of the brain fail to migrate to the cortex and instead form nodules, causing a syndrome called periventricular heterotopia (Figure 16–24B). Interestingly, in addition to binding actin, filamins have been reported to interact with a large number of cellular proteins of great functional diversity, including membrane receptors for signaling molecules, and filamin mutations can also lead to defects in development of bone, the cardiovascular system, and other organs. Thus, filamins may also function as signaling scaffolds by connecting and coordinating a wide variety of cellular processes with the actin cytoskeleton.