1: cAR1-mediated spatiotemporal dynamics of Ras signaling. To reveal the inhibitory mechanism, we monitored spatiotemporal activation of Ras by observing the membrane translocation of a fluorescent probe, active Ras Binding Domain fused to GFP (RBD-GFP) in response to a cAMP gradient. The Ras-activation dynamics we observed indicate that a negative regulator, possibly a RasGAP, is gradually recruited to the membrane and promotes Ras inactivation. In mammalian cells, a RasGAP containing a phospholipid-binding domain has been shown to translocate to the plasma membrane's inner face, deactivate Ras, and thereby inhibit PI3K. We proposed that a similar phospholipid-bound RasGAP is likely to be an important inhibitor in cAR1-mediated chemosensing in D. discoideum. To test this hypothesis, we are studying the roles of RasGAP in chemosensing in D. discoideum. 2: A novel Gbg effector, ElmoE, transduces GPCR signaling to the actin network during chemotaxis. Activation of G-protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into Ga and Gbg subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, Gbg subunits regulate actin assembly and migration, but the protein(s) linking Gbg to the actin cytoskeleton remains unknown. Here, we identified a new Gbg effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE interacts with Gbg and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE serves as the first direct link between chemoattractant GPCRs, G-proteins and the actin cytoskeleton. The pathway, consisting of GPCR, Gbg, Elmo/Dock, Rac, and Arp2/3, spatially guides the growth of dendritic actin networks in pseudopods of eukaryotic cells during chemotaxis (Yan et al Dev. Cell 2012).

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Pan, Miao; Xu, Xuehua; Chen, Yong et al. (2016) Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis. Dev Cell 36:428-39
Cao, Xiumei; Yan, Jianshe; Shu, Shi et al. (2014) Arrestins function in cAR1 GPCR-mediated signaling and cAR1 internalization in the development of D. discoideum. Mol Biol Cell :
Jin, Tian (2013) Gradient sensing during chemotaxis. Curr Opin Cell Biol 25:532-7
Kataria, Rama; Xu, Xuehua; Fusetti, Fabrizia et al. (2013) Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric G proteins and is important for development and chemotaxis. Proc Natl Acad Sci U S A 110:6424-9
Xu, Xuehua; Jin, Tian (2012) A shortcut from GPCR signaling to Rac-mediated actin cytoskeleton through an ELMO/DOCK complex. Small GTPases 3:183-5
Yan, Jianshe; Jin, Tian (2012) Signaling network from GPCR to the actin cytoskeleton during chemotaxis. Bioarchitecture 2:15-18
Yan, Jianshe; Mihaylov, Vassil; Xu, Xuehua et al. (2012) A Gýýýý effector, ElmoE, transduces GPCR signaling to the actin network during chemotaxis. Dev Cell 22:92-103
Jin, Tian (2011) GPCR-controlled chemotaxis in Dictyostelium discoideum. Wiley Interdiscip Rev Syst Biol Med 3:717-27
Yan, Jianshe; Hereld, Dale; Jin, Tian (2010) Chemotaxis: new role for Ras revealed. Protein Cell 1:879-80
Brzostowski, Joseph A; Fey, Petra; Yan, Jianshe et al. (2009) The Elmo family forms an ancient group of actin-regulating proteins. Commun Integr Biol 2:337-40

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