Pathways Regulating Cell Adhesion and Motility

Example 3

The phenotype did not depend specifically on the RasC/TORC2 or PI3K pathways. Rather, signals from multiple pathways impinging on the cytoskeleton can be integrated to generate the phenotype. RAM (Regulator of Adhesion and Motility) mutants were isolated in a screen for regulators of cell morphology and migration. Mutant cells were more spread and adhered more strongly than wild-type cells. Most of the mutants also displayed strong defects in cell motility and chemotaxis. When constitutively active RasC^Q62L was expressed in the RAM mutants, these cells also formed extremely spread cells like those seen in the pten− cell background (FIG. 5). In another example, Rap1 is a small GTPase that controls cell adhesion in a variety of cell types. When constitutively active Rap1A^G12V was expressed in pten− or RAM cells, a similar phenotype was observed.