FIGURE 6-41 Inactivation of the function of a wild-type GTPase by the action of a dominant-negative mutant allele. (a) Small (monomeric) GTPases (purple) are activated by their interaction with a guanine nucleotide exchange factor (GEF), which catalyzes the exchange of GDP for GTP. (b) Introduction of a dominant-negative allele of a small GTPase gene into cultured cells or transgenic animals leads to expression of a mutant GTPase that binds to and inactivates the GEF. As a result, endogenous wild-type copies of the same small GTPase are trapped in the inactive GDP-bound state. A single dominant-negative allele thus causes a loss-of-function phenotype in heterozygotes similar to that seen in homozygotes carrying two recessive loss-of-function alleles.