Biology Reference
In-Depth Information
Figure 14.3 Model of calpain activation in a migrating cell. Indirect evidence suggests that
calpain may be active at the cell's rear where it facilitates focal complex disassembly and
rear retraction
protrusion in a direction away from the chemoattractant, may also potentially
participate during chemotaxis. There has been some recent progress in
understanding how cells migrate directionally in a gradient of chemoattrac-
tant. Although an even distribution of chemoattractant receptor have been
found on the surface of cells during chemotaxis (Jin et al., 2000; Servant et al.,
1999), recent studies has demonstrated that a gradient in chemoattractant
induces an asymmetry in the localization of PIP
3
. In response to a gradient of
chemoattractant PIP
3
localizes to the leading edge of migrating neutrophils
(Servant et al., 2000) (see Chapter 17). The findings suggest that a gradient of
chemoattractant induces localized changes in membrane organization and
recruitment of signalling proteins. We observe a dose-dependent enhancement
of neutrophil chemokinesis or random migration after calpain inhibition
(Lokuta et al., 2003). We also find that at higher concentrations of cell-
permeable inhibitors neutrophil chemotaxis and directional persistence
toward chemoattractant is diminished, supporting a role for calpain in
directional sensing in response to a gradient of chemoattractant. Together, the
findings raise the intriguing possibility that enhanced calpain activity at the
rear of chemotaxing cells may act as a negative signal that serves to re-direct
migration in the direction of chemoattractant (Figure 14.3).
Conclusions
Despite recent progress, our understanding of the mechanisms that regulate
directional migration and the integration of diverse external cues remains
