G protein-coupled receptors detect many different external signals including ones that regulate gene expression and cellular differentiation. While many components of G protein-mediated signal transduction pathways are known, the mechanisms by which different signals regulate specific genes remains to be determined. Pathway specificity is, in part, determined by the G protein G (alpha) subunits, and recent data indicate these subunits play a role in gene regulation in the soil amoebae Dictyostelium. The goal of the proposed research is to test the hypothesis that G (alpha) subunits regulate gene expression through interactions with other signaling components, such as MAP (mitogen-activated protein) kinases. To achieve this goal, the early developmental expression of discoidin (Dsc) in Dictyostelium will be examined in cells lacking the MAP kinase Erk2 and expressing different wild-type or chimeric G (alpha) subunits. In addition, a genetic screen will be used to identify suppressor mutations that rescue pDSC/GFP reporter gene expression from the repression of a chimeric G (alpha) subunit. The suppressor mutations will be created by REMI mutagenesis, allowing genes to be tagged that might function downstream of G (alpha) subunits to regulate gene expression. Additional characterization of suppressor genes will be conducted to verify their function regulating DSC gene expression downstream of G (alpha) subunits in these signaling pathways. These studies will provide significant insights into the signaling mechanisms that control the differentiation of eukaryotic cells. ? ? ?
| Hadwiger, Jeffrey A (2013) Role of the Vps9-domain protein RgfA in Dictyostelium chemotaxis and development. Can J Microbiol 59:22-7 |
| Hadwiger, Jeffrey A; Nguyen, Hoai-Nghia (2011) MAPKs in development: insights from Dictyostelium signaling pathways. Biomol Concepts 2:39-46 |
| Nguyen, Hoai-Nghia; Raisley, Brent; Hadwiger, Jeffrey A (2010) MAP kinases have different functions in Dictyostelium G protein-mediated signaling. Cell Signal 22:836-47 |
| Raisley, Brent; Nguyen, Hoai-Nghia; Hadwiger, Jeffrey A (2010) G{alpha}5 subunit-mediated signalling requires a D-motif and the MAPK ERK1 in Dictyostelium. Microbiology 156:789-97 |
| Nguyen, Hoai-Nghia; Hadwiger, Jeffrey A (2009) The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium. Dev Biol 335:385-95 |
| Hadwiger, Jeffrey A (2007) Developmental morphology and chemotactic responses are dependent on G alpha subunit specificity in Dictyostelium. Dev Biol 312:1-12 |
