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C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis

Phagocytosis, macropinocytosis, and G protein coupled receptor-mediated chemotaxis are Ras-regulated and actin-driven processes. The common regulator for Ras activity in these three processes remains unknown. Here, we show that C2GAP2, a Ras GTPase activating protein, highly expressed in the vegetat...

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Autores principales: Xu, Xuehua, Pots, Henderikus, Gilsbach, Bernd K., Parsons, Dustin, Veltman, Douwe M., Ramachandra, Sharmila G., Li, Haoran, Kortholt, Arjan, Jin, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745196/
https://www.ncbi.nlm.nih.gov/pubmed/36524124
http://dx.doi.org/10.3389/fimmu.2022.1075386
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author Xu, Xuehua
Pots, Henderikus
Gilsbach, Bernd K.
Parsons, Dustin
Veltman, Douwe M.
Ramachandra, Sharmila G.
Li, Haoran
Kortholt, Arjan
Jin, Tian
author_facet Xu, Xuehua
Pots, Henderikus
Gilsbach, Bernd K.
Parsons, Dustin
Veltman, Douwe M.
Ramachandra, Sharmila G.
Li, Haoran
Kortholt, Arjan
Jin, Tian
author_sort Xu, Xuehua
collection PubMed
description Phagocytosis, macropinocytosis, and G protein coupled receptor-mediated chemotaxis are Ras-regulated and actin-driven processes. The common regulator for Ras activity in these three processes remains unknown. Here, we show that C2GAP2, a Ras GTPase activating protein, highly expressed in the vegetative growth state in model organism Dictyostelium. C2GAP2 localizes at the leading edge of chemotaxing cells, phagosomes during phagocytosis, and macropinosomes during micropinocytosis. c2gapB− cells lacking C2GAP2 displayed increased Ras activation upon folic acid stimulation and subsequent impaired chemotaxis in the folic acid gradient. In addition, c2gaB(-) cells have elevated phagocytosis and macropinocytosis, which subsequently results in faster cell growth. C2GAP2 binds multiple phospholipids on the plasma membrane and the membrane recruitment of C2GAP2 requires calcium. Taken together, we show a shared negative regulator of Ras signaling that mediates Ras signaling for chemotaxis, phagocytosis, and macropinocytosis.
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spelling pubmed-97451962022-12-14 C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis Xu, Xuehua Pots, Henderikus Gilsbach, Bernd K. Parsons, Dustin Veltman, Douwe M. Ramachandra, Sharmila G. Li, Haoran Kortholt, Arjan Jin, Tian Front Immunol Immunology Phagocytosis, macropinocytosis, and G protein coupled receptor-mediated chemotaxis are Ras-regulated and actin-driven processes. The common regulator for Ras activity in these three processes remains unknown. Here, we show that C2GAP2, a Ras GTPase activating protein, highly expressed in the vegetative growth state in model organism Dictyostelium. C2GAP2 localizes at the leading edge of chemotaxing cells, phagosomes during phagocytosis, and macropinosomes during micropinocytosis. c2gapB− cells lacking C2GAP2 displayed increased Ras activation upon folic acid stimulation and subsequent impaired chemotaxis in the folic acid gradient. In addition, c2gaB(-) cells have elevated phagocytosis and macropinocytosis, which subsequently results in faster cell growth. C2GAP2 binds multiple phospholipids on the plasma membrane and the membrane recruitment of C2GAP2 requires calcium. Taken together, we show a shared negative regulator of Ras signaling that mediates Ras signaling for chemotaxis, phagocytosis, and macropinocytosis. Frontiers Media S.A. 2022-11-29 /pmc/articles/PMC9745196/ /pubmed/36524124 http://dx.doi.org/10.3389/fimmu.2022.1075386 Text en Copyright © 2022 Xu, Pots, Gilsbach, Parsons, Veltman, Ramachandra, Li, Kortholt and Jin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Xu, Xuehua
Pots, Henderikus
Gilsbach, Bernd K.
Parsons, Dustin
Veltman, Douwe M.
Ramachandra, Sharmila G.
Li, Haoran
Kortholt, Arjan
Jin, Tian
C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title_full C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title_fullStr C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title_full_unstemmed C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title_short C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
title_sort c2gap2 is a common regulator of ras signaling for chemotaxis, phagocytosis, and macropinocytosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745196/
https://www.ncbi.nlm.nih.gov/pubmed/36524124
http://dx.doi.org/10.3389/fimmu.2022.1075386
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