Staurosporine induces lamellipodial widening in locomoting fish keratocytes by abolishing the gradient from radial extension of leading edge

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Fish epidermal keratocytes locomote along surfaces without overall cell size or shape changes, as kinematically described by the graded radial extension (GRE) model. We found that the cell size increased during locomotion after the addition of a low dose of staurosporine or K-252a, broad-spectrum protein-serine/threonine kinase inhibitors. Quantitative shape analysis showed that the cell size increase resulted from an increase in lamellipodial width, the maximal length perpendicular to the direction of the cell locomotion, whereas the lamellipodial length, along the locomotion direction, remained constant. Importantly, the gradient of radial extension in the leading edge disappeared during lamellipodial width increase. These results suggest that a special mechanism for producing graded radial extension of lamellipodia exists to keep cell size constant, and that a protein-serine/threonine kinase plays an important role in regulating this mechanism.