GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis

Xuehua Xu; Xi Wen; Douwe M. Veltman; Ineke Keizer-Gunnink; Henderikus Pots; arjan kortholt; Tian Jin

doi:10.1073/pnas.1703208114

GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis

Xuehua Xu, Xi Wen, Douwe M. Veltman, Ineke Keizer-Gunnink, Henderikus Pots, arjan kortholt, Tian Jin

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Significance Eukaryotic cells migrate through a gradient with a huge concentration range of chemoattractant stimuli by employing “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. Many models agree on the “temporal adaptation”: a rapid “excitation” that triggers cellular responses and a temporally delayed “inhibition” that terminates the responses to reach adaptation. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. In the present study, we showed that GPCR-activated Ras negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis.

Original language	English
Pages (from-to)	E10092-E10101
Journal	Proceedings of the National Academy of Sciences
Volume	114
Issue number	47
DOIs	https://doi.org/10.1073/pnas.1703208114
Publication status	Published - 21 Nov 2017
Externally published	Yes

Funding

ACKNOWLEDGMENTS. We thank Drs. Xinzhuan Su and Joseph Brzostowski for their critical reading of the article; Wei Quan for his help with chemotaxis video analysis; and Dr. Peter van Haastert, Susanne Terheyden, and Kavya Prasad for assistance with the biochemical experiments. This work was supported by the intramural fund of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the American Heart Association (AHA0930127N).

Funders	Funder number
National Institutes of Health
National Institute of Allergy and Infectious Diseases	ZIAAI000916
American Heart Association	AHA0930127N

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title = "GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis",

abstract = "Significance Eukaryotic cells migrate through a gradient with a huge concentration range of chemoattractant stimuli by employing “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. Many models agree on the “temporal adaptation”: a rapid “excitation” that triggers cellular responses and a temporally delayed “inhibition” that terminates the responses to reach adaptation. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. In the present study, we showed that GPCR-activated Ras negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis.",

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AU - Wen, Xi

AU - Veltman, Douwe M.

AU - Keizer-Gunnink, Ineke

AU - Pots, Henderikus

AU - kortholt, arjan

AU - Jin, Tian

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AB - Significance Eukaryotic cells migrate through a gradient with a huge concentration range of chemoattractant stimuli by employing “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. Many models agree on the “temporal adaptation”: a rapid “excitation” that triggers cellular responses and a temporally delayed “inhibition” that terminates the responses to reach adaptation. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. In the present study, we showed that GPCR-activated Ras negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis.

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JF - Proceedings of the National Academy of Sciences

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ER -

GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis

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