| dc.creator |
Wen, Xi |
|
| dc.creator |
Xu, Xuehua |
|
| dc.creator |
Jin, Tian |
|
| dc.creator |
Kortholt, Arjan |
|
| dc.creator |
Keizer-Gunnink, Ineke |
|
| dc.creator |
Pots, Henderikus |
|
| dc.creator |
Veltman, Douwe M. |
|
| dc.date |
2017-11-01T00:00:00Z |
|
| dc.date.accessioned |
2023-01-09T12:02:40Z |
|
| dc.date.available |
2023-01-09T12:02:40Z |
|
| dc.identifier |
513ce94e-706d-41a2-bbb8-742f5f375670 |
|
| dc.identifier |
10.1073/pnas.1703208114 |
|
| dc.identifier |
https://avesis.sdu.edu.tr/publication/details/513ce94e-706d-41a2-bbb8-742f5f375670/oai |
|
| dc.identifier.uri |
http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/97842 |
|
| dc.description |
Eukaryotic cells chemotax in a wide range of chemoattractant concentration gradients, and thus need inhibitory processes that terminate cell responses to reach adaptation while maintaining sensitivity to higher-concentration stimuli. However, the molecular mechanisms underlying inhibitory processes are still poorly understood. Here, we reveal a locally controlled inhibitory process in a GPCR-mediated signaling network for chemotaxis in Dictyoste-lium discoideum. We identified a negative regulator of Ras signaling, C2GAP1, which localizes at the leading edge of chemotaxing cells and is activated by and essential for GPCR-mediated Ras signaling. We show that both C2 and GAP domains are required for the membrane targeting of C2GAP1, and that GPCR-triggered Ras activation is necessary to recruit C2GAP1 from the cytosol and retains it on the membrane to locally inhibit Ras signaling. C2GAP1-deficient c2gapA(- )cells have altered Ras activation that results in impaired gradient sensing, excessive polymerization of F actin, and subsequent defective chemotaxis. Remarkably, these cellular defects of c2gapA(-) cells are chemoattractant concentration dependent. Thus, we have uncovered an inhibitory mechanism required for adaptation and long-range chemotaxis. |
|
| dc.language |
eng |
|
| dc.rights |
info:eu-repo/semantics/closedAccess |
|
| dc.title |
GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis |
|
| dc.type |
info:eu-repo/semantics/article |
|