Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins

Abstract

The Ras-related GTPases Rap1a and 1b have been implicated in multiple biological events including cell adhesion, free radical production and cancer. To gain a better understanding of Rap1 function in mammalian physiology we deleted the Rap1a gene. Although loss of Rap1a expression did not initially affect mouse size or viability, upon backcross into C57Bl/6J mice some Rap1a −/− embryos died in utero. T cell, B cell or myeloid cell development was not disrupted in Rap1a −/− mice. However, macrophages from Rap1a null mice exhibited increased haptotaxis on fibronectin and vitronectin matrices that correlated with decreased adhesion. Chemotaxis of lymphoid and myeloid cells in response to CXCL12 or CCL21 was significantly reduced. In contrast, an increase in Fc receptor-mediated phagocytosis was observed. Since Rap1a was previously copurified with the