Figure 16–24 Filamin cross-links actin filaments into a three-dimensional network and is required for normal neuronal migration. (A) Each filamin homodimer is about 160 nm long when fully extended and forms a flexible, high-angle link between two adjacent actin filaments. A set of actin filaments cross-linked by filamin forms a mechanically strong web or gel. (B) Magnetic resonance imaging of a normal human brain (left) and of a patient with periventricular heterotopia (right) caused by mutation in the filamin A gene. In contrast to the smooth ventricular surface in the normal brain, a rough zone of cortical neurons (arrowheads) is seen along the lateral walls of the ventricles, representing neurons that have failed to migrate to the cortex during brain development. Remarkably, although many neurons are not in the right place, the intelligence of affected individuals is frequently normal or only mildly compromised, and the major clinical syndrome is epilepsy that often starts in the second decade of life. (B, adapted from
Y. Feng and C.A. Walsh, Nat. Cell Biol. 6:1034–1038, 2004. With permission  from Macmillan Publishers Ltd.)
Figure 16–25 The actin-based movement of Listeria monocytogenes. (A) Fluorescence micrograph of an infected cell that has been stained to reveal bacteria in red and actin filaments in green. Note the cometlike tail of actin filaments behind each moving bacterium. Regions of overlap between red and green fluorescence appear yellow. (B) Listeria motility can be reconstituted in a test tube with ATP and just four purified proteins: actin, Arp 2/3 complex, capping protein, and cofilin. This micrograph shows the dense actin tails behind bacteria (black). (C) The ActA protein on the bacterial surface activates the Arp 2/3 complex to nucleate new filament assembly along the sides of existing filaments. Filaments grow at their plus end until capped by capping protein. Actin is recycled through the action of cofilin, which enhances depolymerization at the minus ends of the filaments. By this mechanism, polymerization is focused at the rear surface of the bacterium, propelling it forward (see Movie 23.7). (A, courtesy of Julie Theriot and Tim Mitchison; B, from T.P. Loisel et al., Nature 401:613–616, 1999. With permission from Macmillan Publishers Ltd.) cytoplasm at rates of up to 1 μm/sec, leaving behind a long actin “comet tail” (Figure 16–25; see also Figures 23–28 and 23–29). This motility can be reconstituted in a test tube by adding the bacteria to a mixture of pure actin, Arp 2/3 complex, cofilin, and capping protein, illustrating how actin polymerization dynamics generate movement through spatial regulation of filament assembly and disassembly. As we shall see, actin-based movement of this sort also underlies membrane protrusion at the leading edge of motile cells.