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

TL;DR

This paper explores how IqgC, a protein in Dictyostelium discoideum, regulates actin dynamics and cell behavior through its interactions with Ras GTPases.

Contribution

The paper identifies IqgC as a RasGAP with unique domain functions and roles in cell adhesion and migration.

Findings

IqgC suppresses macroendocytosis and supports cell adhesion and migration.

The RasGAP domain localizes IqgC to macroendocytic cups, while the RGCt domain targets it to focal adhesions.

IqgC interacts with Ras, Rab, and Rap GTPases but only promotes GTPase activity for Ras.

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.

IqgC is a RasGAP from Dictyostelium discoideum. IqgC binds RasG via its RasGAP domain and deactivates it on macroendocytic cups, thereby suppressing the uptake of fluid and particles. IqgC has a positive effect on cell‐substratum adhesion, and its RGCt domain is required for recruitment to ventral foci. IqgC also interacts with RapA, and both GTPases have a stimulatory effect on adhesion.

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