M.D., National Yang-Ming Medical College
Ph.D., BCMB program, Johns Hopkins University School of Medicine
Mechanism and regulation of amoeboid chemotaxis
Amoeboid chemotaxis is of fundamental importance in cell-mediated immunity as well as tumor invasion and metastasis. Dictyostelium provides an excellent model system for studying chemotaxis since this organism spends most of its life cycle as chemotactic amoeboid cells and chemotaxis plays a pivotal role during its starvation-induced developmental program. We perform mutagenesis in Dictyostelium, screen for mutants with aberrant chemotactic behaviors, and from the collected mutants, identify and clone the genes responsible for the phenotype. Further analyses of the identified novel genes and their homologs in mammals should provide more insights into the molecular mechanism and regulation of eukaryotic chemotaxis.
Functions of Pianissimo homologs in TOR signaling pathway
Pianissimo (Pia) was first identified in Dictyostelium as a novel cytosolic protein involved in cAMP signaling pathway. Pia-like proteins exist in a diverse organisms ranging from yeast to mammals. Using a combination of molecular and genetic methods, we have found that the Saccharomyces cerevisiae homolog (Tsc11p or Avo3p) is involved in modulating cell integrity and interacts functionally with the target of rapamycin (Tor2p) signaling pathway. In yeast, Tor2p controls cell growth and regulates the cell cycle-dependent organization of actin cytoskeleton. Further studies are underway to elucidate the role of Tsc11p in these signaling pathways.
1. Chen, M.Y., Insall, R. H. and Devreotes, P. N. (1996) Signaling through chemoattractant receptors in Dictyostelium. Trends Genet. 12, 52-57.
2. Chen, M.Y., Long, Y. and Devreotes, P. N. (1997) A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the twelve transmembrane domain adenylyl cyclase in Dictyostelium. Genes Dev. 11, 3218-3231.
3. Pang, T.L., Wang, C.Y., Hsu, C.L., Chen, M.Y., and Lin, J.J. (2003) Exposure of single-stranded telomeric DNA causes G2/M cell cycle arrest in Saccharomyces cerevisiae. J. Biol. Chem. 278, 9318-9321.
4. Ho, H.L., Shiau, Y.S., and Chen, M.Y. (2005) The Saccharomyces cerevisiae PIA1/TSC11/AVO3 gene participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Curr. Genet. 47(5), 273-288.
5. Pang, T.L., Wu, C.J., Chen, P.A., Weng, Y.L., and Chen, M.Y. (2006) Developmental regulation and differential roles of novel LARGE glycosyltransferase-like genes in Dictyostelium discoideum. (Manuscript submitted).
6. Pang, T.L. and Chen, M.Y. (2006) A novel STARS-like protein regulates actin organization and cAMP-mediated chemotaxis in Dictyostelium discoideum. (Manuscript in preparation).
7. Li, H.Y. and Chen, M.Y. (2006) The role of RhoGAPs in Tsc11p signaling in Saccharomyces cerevisiae. (Manuscript in preparation).