Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families.

Abstract

In addition to transmitting receptor-mediated signals to adjust the gene expression profile of the cell, small GTPases of the Ras family also control the remodelling of the actin cytoskeleton. The conversion of Ras GTPases from their active to their inactive form is controlled by Ras GTPase-activating proteins (RasGAPs). IqgC, a RasGAP from Dictyostelium discoideum, was originally assigned to the IQGAP family, but its sequence and recent functional analyses show that IqgC is more closely related to RasGAPs from the GAP1 family of fungi. IqgC has two prominent domains, a RasGAP domain and a C-terminal RGCt domain, and interacts with Ras, Rab and Rap GTPases, but shows GTPase-promoting activity only towards Ras. IqgC suppresses macroendocytosis but supports cell-substratum adhesion and directed cell migration. Its localisation to macroendocytic cups is mediated by the RasGAP domain, whereas its localisation in ventral focal adhesions is mediated by the RGCt domain. We hypothesise that IqgC plays an important role in the balance between the competing feeding and migratory behaviour of amoeboid D. discoideum cells.