We have two projects. 1. How does CXCR4 receptor signaling to Elmo/Dock complex leading to actin cytoskeleton? Our study in D. discoideum revealed a novel pathway linking G-protein subunits directly to Elmo/Dock complex. We are in the process to investigate whether this is evolutionarily conserved in chemokine receptor-controlled cell migration in human. 2. The role of beta- arrestin in neutrophil chemotaxis. It is known that activated chemokine GPCRs interact with beta-arrestin, which brings signaling components and activates pathways independent of G-proteins. It has been suggested that beta-arrestin signaling plays a role in cell migration, but the molecular mechanisms underlining this process are not known. We are in the process to study these mechanisms using neutrophils.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$415,478
Indirect Cost
City
State
Country
Zip Code
Xu, Xuehua; Yun, Michelle; Wen, Xi et al. (2016) Quantitative Monitoring Spatiotemporal Activation of Ras and PKD1 Using Confocal Fluorescent Microscopy. Methods Mol Biol 1407:307-23
Gera, Nidhi; Swanson, Kenneth D; Jin, Tian (2016) β-Arrestin 1-dependent regulation of Rap2 is required for fMLP-stimulated chemotaxis in neutrophil-like HL-60 cells. J Leukoc Biol :
Wang, Youhong; Xu, Xuehua; Pan, Miao et al. (2016) ELMO1 Directly Interacts with Gβγ Subunit to Transduce GPCR Signaling to Rac1 Activation in Chemotaxis. J Cancer 7:973-83
Xu, Xuehua; Gera, Nidhi; Li, Hongyan et al. (2015) GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis. Mol Biol Cell 26:874-86
Li, Hongyan; Yang, Lei; Fu, Hui et al. (2013) Association between Gýýi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nat Commun 4:1706
Guo, Jia; Xu, Xuehua; Rasheed, Taban K et al. (2013) Genistein interferes with SDF-1- and HIV-mediated actin dynamics and inhibits HIV infection of resting CD4 T cells. Retrovirology 10:62
Guo, Jia; Xu, Xuehua; Yuan, Wen et al. (2012) HIV gp120 is an aberrant chemoattractant for blood resting CD4 T cells. Curr HIV Res 10:636-42
Chen, Yan; Yue, Shen; Xie, Lu et al. (2011) Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium. J Biol Chem 286:13502-11
Kim, Jung-Sik; Xu, Xuehua; Li, Huifang et al. (2011) Mechanistic analysis of a DNA damage-induced, PTEN-dependent size checkpoint in human cells. Mol Cell Biol 31:2756-71