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Figure 14.2 Biphasic dependence of cell migration speed on calpain activity. Neutrophils
have high endogenous calpain activation and treatment with cell permeable calpain
inhibitors induces cell adhesion and random migration. In contrast, fibroblasts have a
medium amount of calpain activity in adherent cells that is supportive of cell migration.
Calpain inhibition results in an inhibition of rear retraction and migration speed. At its
extreme, calpain inhibition can reduce cell spreading as depicted. This is most notable in
lymphocytes and endothelial cells
Our recent studies also support an important role for calpain in
mechanosensing and re-orientation in response to cell-cell contact. Fibro-
blasts normally re-orientate after contact with a neighbouring cell with
protrusion away from the contacting cell. In Capn4 7/7 fibroblasts or after
calpain inhibition in CHOK1 cells, we find that cells continue to migrate over
contacting cells without contact inhibition or re-orientation after contact
(Perrin, unpublished observation).
Recent observations also support a role for calpain in regulating neutrophil
chemotaxis (Lokuta et al., 2003). Chemotaxis is directional migration in
response to a gradient of chemoattractant (Allen et al., 1998; Devreotes and
Zigmond, 1988; Zigmond et al., 1981). The gradients that stimulate directional
cell migration may be very shallow, with as little as a 2% gradient of
chemoattractant between the cell front and rear (Parent and Devreotes, 1999).
Recent evidence suggests that shallow gradients of chemoattractant are
translated into larger gradients of intracellular signalling proteins that are
required for cell polarization and directional cell migration. It is not clear if
positive signals alone are su cient for the optimum response and chemotaxis
of cells to external signals. The participation of negative signals, that inhibit
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