Rap1, a mercenary among the Ras-like GTPases

The small Ras-like GTPase Rap1 is an evolutionary conserved protein that originally gained interest because of its capacity to revert the morphological phenotype of Ras-transformed fibroblasts. Rap1 is regulated by a large number of stimuli that include growth factors and cytokines, but also physical force and osmotic stress. Downstream of Rap1, a plethora of effector molecules has been proposed on the basis of biochemical studies. Here, we present an overview of genetic studies on Rap1 in various model organisms and relate the observed phenotypes to in vitro studies. The picture that emerges is one in which Rap1 is a versatile regulator of morphogenesis, by regulating diverse processes that include establishment of cellular polarity, cell-matrix interactions and cell-cell adhesion. Surprisingly, genetic experiments indicate that in the various model organisms, Rap1 uses distinct effector molecules that impinge upon the actin cytoskeleton and adhesion molecules.