cell migration extra reading Flashcards
undirectional motion by lamellipodia
Maintenance of unidirectional motion by lamellipodia is thought to require the cooperation and mechanical integration of several factors. Filament nucleation is localized at the leading edge, with new actin filament growth occurring primarily in that location to push the plasma membrane forward. Most filament depolymerization occurs at sites located well behind the leading edge. Because cofilin (see Figure 16– 20) binds cooperatively and preferentially to actin filaments containing ADP-actin (the D form), the new T-form filaments generated at the leading edge should be resistant to depolymerization by cofilin ( Figure 16– 79 ). As the filaments age and ATP hydrolysis proceeds, cofilin can efficiently disassemble the older filaments. Thus, the delayed ATP hydrolysis by filamentous actin is thought to provide the basis for a mechanism that maintains an efficient, unidirectional treadmilling process in the lamellipodium ( Figure 16– 80 ); it also explains the intracellular movement of MBoC6 bacterial m16.89/16.81 pathogens such as Listeria (see Figure 16– 25). Myosin Contraction and Cell Adhesion Allow Cells to Pull Themselves Forward Forces generated by actin filament polymerization at the front of a migrating cell are transmitted to the underlying substratum to drive cell motion. For the leading Figure 16– 79 Cofilin in lamellipodia. (A) A keratocyte with actin filaments labeled in red by fluorescent phalloidin, and cofilin labeled in green with a fluorescent antibody. Although the dense actin meshwork reaches all the way through the lamellipodium, cofilin is not found at the very leading edge. (B) Close-up view of the region marked with the white rectangle in (A). The actin filaments closest to the leading edge, which are also the ones that have formed most recently and that are most likely to contain ATP-actin (rather than ADP-actin), are generally not associated with cofilin. (From T. Svitkina and G. Borisy, J. Cell Biol. 145:1009– 1026, 1999. With permission from the authors.)
myosin’s role
The processes contributing to migration are therefore tightly regulated in space and time, with actin polymerization, dynamic adhesions, and myosin contraction being employed to coordinate movement. Myosin II operates in at least two ways to assist cell migration. The first is by helping to connect the actin cytoskeleton to the substratum through integrin-mediated adhesions. Forces generated by both actin polymerization and myosin activity create tension at attachment sites, promoting their maturation into focal adhesions , which are dynamic assemblies of structural and signaling proteins that link the migrating cell to the extracellular matrix (see Figure 19– 59). A second mechanism involves bipolar myosin II filaments, which associate with the actin filaments at the rear of the lamellipodium and pull them into a new orientation— from nearly perpendicular to the leading edge to almost parallel to the leading edge. This sarcomere-like contraction prevents protrusion, and it pinches in the sides of the locomoting lamellipodium, helping to gather in the sides of the cell as it moves forward ( Figure 16– 81 ). Actin-mediated protrusions can only push the leading edge of the cell forward if there are strong interactions between the actin network and the focal adhesions that link the cell to the substrate. When these interactions are disengaged, polymerization pressure at the leading edge and myosin-dependent contraction cause the actin network to slip back, resulting in a phenomenon known as retrograde flow ( Figure
