IQGAP-related protein IqgC suppresses Ras signaling during large-scale endocytosis

Marinović, Maja; Mijanović, Lucija; Šoštar, Marko; Vizovišek, Matej; Junemann, Alexander; Fonović, Marko; Turk, Boris; Weber, Igor; Faix, Jan; Filić, Vedrana (2019) IQGAP-related protein IqgC suppresses Ras signaling during large-scale endocytosis. Proceedings of the National Academy of Sciences, 116 (4). pp. 1289-1298. ISSN 0027-8424

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Official URL: https://www.pnas.org/content/116/4/1289

Abstract

Macropinocytosis and phagocytosis are evolutionarily conserved forms of bulk endocytosis used by cells to ingest large volumes of fluid and solid particles, respectively. Both processes are regulated by Ras signaling, which is precisely controlled by mechanisms involving Ras GTPase activating proteins (RasGAPs) responsible for terminating Ras activity on early endosomes. While regulation of Ras signaling during large-scale endocytosis in WT Dictyostelium has been, for the most part, attributed to the Dictyostelium ortholog of human RasGAP NF1, in commonly used axenic laboratory strains, this gene is mutated and inactive. Moreover, none of the RasGAPs characterized so far have been implicated in the regulation of Ras signaling in large-scale endocytosis in axenic strains. In this study, we establish, using biochemical approaches and complementation assays in live cells, that Dictyostelium IQGAP-related protein IqgC interacts with active RasG and exhibits RasGAP activity toward this GTPase. Analyses of iqgC− and IqgC-overexpressing cells further revealed participation of this GAP in the regulation of both types of large-scale endocytosis and in cytokinesis. Moreover, given the localization of IqgC to phagosomes and, most prominently, to macropinosomes, we propose IqgC acting as a RasG-specific GAP in large-scale endocytosis. The data presented here functionally distinguish IqgC from other members of the Dictyostelium IQGAP family and call for repositioning of this genuine RasGAP outside of the IQGAP group.

Item Type:

Article

Additional Information:

M.S. and V.F. were supported by FP7-REGPOT-2012-2013-1 Grant Agreement 316289-InnoMol. M.M. was supported by the European Social Fund under the project Interdisciplinary Research in Cell Biology-INTERBIO (to I.W.). L.M. was supported in part by the "Young Researchers' Career Development Project-Training of Doctoral Students" of the Croatian Science Foundation funded by the European Union from the European Social Fund (to I.W.). For support, we thank Deutche Forschungsgemeinschaft (DFG) Grant Fa330/6 2 (to J.F.) and the Slovenian Research Agency [Grants P1-0140 (to B.T.) and J1-5449 (to M.F.)].

Uncontrolled Keywords:

IqgC; RasGAP; Ras; macropinocytosis; phagocytosis

Subjects:

NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology

Divisions:

Division of Molecular Biology

Projects: