IqgC is a potent regulator of macropinocytosis in the presence of NF1 and its loading to macropinosomes is dependent on RasG

Putar, Darija; Čizmar, Anja; Chao, Xiaoting; Šimić, Marija; Šoštar, Marko; Ćutić, Tamara; Mijanović, Lucija; Smolko, Ana; Tu, Hui; Cosson, Pierre; Weber, Igor; Cai, Huaqing; Filić, Vedrana (2024) IqgC is a potent regulator of macropinocytosis in the presence of NF1 and its loading to macropinosomes is dependent on RasG. Open Biology, 14 (1). ISSN 2046-2441

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Abstract

RasG is a major regulator of macropinocytosis in Dictyostelium discoideum. Its activity is under the control of an IQGAP-related protein, IqgC, which acts as a RasG-specific GAP (GTPase activating protein). IqgC colocalizes with the active Ras at the macropinosome membrane during its formation and for some time after the cup closure. However, the loss of IqgC induces only a minor enhancement of fluid uptake in axenic cells that already lack another RasGAP, NF1. Here, we show that IqgC plays an important role in the regulation of macropinocytosis in the presence of NF1 by restricting the size of macropinosomes. We further provide evidence that interaction with RasG is indispensable for the recruitment of IqgC to forming macropinocytic cups. We also demonstrate that IqgC interacts with another small GTPase from the Ras superfamily, Rab5A, but is not a GAP for Rab5A. Since mammalian Rab5 plays a key role in early endosome maturation, we hypothesized that IqgC could be involved in macropinosome maturation via its interaction with Rab5A. Although an excessive amount of Rab5A reduces the RasGAP activity of IqgC in vitro and correlates with IqgC dissociation from endosomes in vivo, the physiological significance of the Rab5A–IqgC interaction remains elusive.

Item Type:	Article
Uncontrolled Keywords:	IqgC; Ras; NF1; Rab5; macropinocytosis; Dictyostelium
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Regulacija endocitoze na velikoj skali pomoću IQGAP proteinima srodnih proteina IqgC i IqgD-RegEndIqCD Vedrana Filić Mileta IP-2020-02-1572 HRZZ Phagocytosis and Macropinocytosis, a mechanistic view- Igor Weber 180584 HRZZ
Depositing User:	Ivana Vuglec
Date Deposited:	25 Mar 2026 11:59
URI:	http://fulir.irb.hr/id/eprint/11473
DOI:	10.1098/rsob.230372

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