RESCUE OF THE MUTANT PHENOTYPE BY REEXPRESSION OF FULL-LENGTH VINCULIN IN NULL F9 CELLS - EFFECTS ON CELL LOCOMOTION BY DOMAIN DELETED VINCULIN

Vinculin plays a role in signaling between integrins and the actin cyt oskeleton, We reported earlier that F9-derived cells lacking vinculin are less spread, less adhesive, and move two times faster than wild-ty pe F9 cells. Expression of intact vinculin in null cells restored all wild-type characteristics. In contrast, expression of the head (90 kDa ) fragment exaggerated mutant characteristics, especially locomotion, which was double that of vinculin null cells, Expression of the tail d omain also had a marked effect on locomotion in the opposite direction , reducing it to very low levels, The expression of the head plus tail domains together (no covalent attachment) effected a partial rescue t owards wild-type phenotype, thus indicating that reexpressed polypepti des may be in their correct location and are interacting normally Ther efore, we conclude that: (1) the head domain is part of the locomotory force of the cell, modulated by the tail, and driven by the integrin/ matrix connection; (2) intact vinculin is required for normal regulati on of cell behavior, suggesting that vinculin head-tail interactions c ontrol cell adhesion, spreading, lamellipodia formation and locomotion .