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

Proc. Natl. Acad. Sci. U.S.A.2019 Jan 22;116(4):1289-1298. Epub 2019 Jan 08
Maja Marinović 1 , Lucija Mijanović 1 , Marko Šoštar 1 , Matej Vizovišek 2 , Alexander Junemann 3 , Marko Fonović 4 , Boris Turk 5 , Igor Weber 1 , Jan Faix 3 , Vedrana Filić 6
Maja Marinović 1 , Lucija Mijanović 1 , Marko Šoštar 1 , Matej Vizovišek 2 , Alexander Junemann 3 , Marko Fonović 4 , Boris Turk 5 , Igor Weber 1 , Jan Faix 3 , Vedrana Filić 6
+ et al

[No authors listed]

Author information
  • 1 Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
  • 2 Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia.
  • 3 Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany.
  • 4 Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, SI-1000 Ljubljana, Slovenia.
  • 5 Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
  • 6 Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia; vedrana.filic@irb.hr.

摘要


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.

KEYWORDS: IqgC, Ras, RasGAP, macropinocytosis, phagocytosis