Biology Reference
In-Depth Information
disassembly in both stationary and migratory cells (Zamir et al., 2000). To
migrate, cells must coordinately assemble and disassemble integrin-containing
adhesive contacts (Huttenlocher et al., 1995; Lauffenburger and Horwitz,
1996). While progress has been made in understanding mechanisms involved
in cell migration, we still have a limited understanding of how regulated
adhesive complex assembly and disassembly occurs and contributes to
directional cell migration. This chapter focuses on the mechanisms of
integrin-mediated cell migration and the role that the calcium-dependent
protease calpain plays in this process.
Basic steps of cell movement
Cell migration requires a regulated and dynamic interaction between the cell
and its surrounding substrate. To migrate cells respond to directional cues and
extend a leading edge, lamellipodia or filopodia, which stabilizes in the
direction of cell movement. For cell translocation to occur, the leading edge
of the cell stabilizes an adhesive complex, which generates the force
and traction required for cell movement. Subsequently, the cell must release
adhesions at the rear to allow for directional progress. Cell migration
may therefore be separated into distinct stages: (1) membrane protrusion with
stabilization of cell-substratum adhesion; (2) generation of contractile force
and (3) detachment at the cell's rear (Stossel, 1993). The classic three-step
migration pattern, i.e., with distinct cell protrusion, cell body contraction and
rear detachment, describes the migration patterns of fibroblasts. Although
representative of many cell types, the mechanisms that govern the movement
of the more rapidly moving cells of the immune system, such as neutrophils,
appear to be distinct. In contrast to fibroblasts, neutrophils e
ciently
coordinate adhesion formation at the cell front and rear release, thereby
demonstrating a gliding movement (Cox and Huttenlocher, 1998).
External factors that regulate cell migration
Cell migration involves the integration of external cues, including both
migration-promoting and migration-inhibiting signals. The external cues that
modulate cell motility are diverse and include growth factors, extracellular
matrix components and cell-cell interactions. The extracellular and growth
factor environment in the adult organisms is generally migration-inhibiting,
with the majority of cells non-migratory. However, in response to perturba-
tions, such as tissue wounding, the extracellular environment may become
permissive and contain migration-promoting signals that stimulate the
migration of fibroblasts and other cell types. It is important to consider that
