TY - JOUR
T1 - C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
AU - Xu, Xuehua
AU - Pots, Henderikus
AU - Gilsbach, Bernd K
AU - Parsons, Dustin
AU - Veltman, Douwe M
AU - Ramachandra, Sharmila G
AU - Li, Haoran
AU - Kortholt, Arjan
AU - Jin, Tian
N1 - Funding Information:
This work was supported by the NIH Intramural Fund from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Publisher Copyright:
Copyright © 2022 Xu, Pots, Gilsbach, Parsons, Veltman, Ramachandra, Li, Kortholt and Jin.
PY - 2022/11/29
Y1 - 2022/11/29
N2 - 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.
AB - 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.
KW - Dictyostelium/metabolism
KW - Chemotaxis
KW - Pinocytosis/physiology
KW - Phagocytosis
KW - Folic Acid
KW - chemotaxis
KW - G protein coupled receptor
KW - GTPase activating proteins (GAPs)
KW - macropinocytosis
KW - model organism dictyostelium
KW - phagocytosis
KW - ras
U2 - 10.3389/fimmu.2022.1075386
DO - 10.3389/fimmu.2022.1075386
M3 - Article
C2 - 36524124
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1075386
ER -