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Peter Devreotes

Department Affiliation Primary: Cell Biology
Secondary: Biological Chemistry
Rank Faculty
Phone Numbers Office: 410-955-3225
Lab: 410-955-4699
Fax: 410-614-9461
Email pnd@jhmi.edu
School of Medicine Address JHU School of Medicine
725 N. Wolfe St., 114 WBSB
Baltimore, MD 21205
Lab Web Link http://www.hopkinsmedicine.org/cellbio/devreotes/
   
Peter Devreotes

Research Topic: Genetic analysis of chemotaxis in eukaryotic cells


Chemotaxis plays a key role in immune response, wound healing, angiogenesis, and embryogenesis. Research in Dictyostelium discoideum has shown that chemoattractants, like many hormones, neurotransmitters, and odorants are sensed by receptors that activate heterotrimeric G-proteins and rapidly trigger a unique network of signaling pathways. Our strategy is to use the genetics of Dictyostelium to discover mechanisms by which cells sense chemical gradients and to apply this information to other eukaryotic cells such as human neutrophils.

Directional cues cause the enzymes that synthesize and degrade PI(3,4,5)P3 to translocate to the membrane at the front and rear of the cell, respectively. Local accumulation of PIP3 directs pseudopod extension at the leading edge. Signaling proceeds through activation of protein kinases ß and requires components of the Tor complex 2. By screening gene-tagged cell lines for mutants with phenotypes similar to those lacking the known signal transduction components, we are identifying novel genes involved in these pathways.


Publications:


Wu, L., Valkema, R., Van Haastert, P.J.M. and Devreotes, P.N. (1995) The G-protein ß-subunit is essential for multiple responses to chemoattractants in Dictyostelium. J Cell Biol 129, 1667-1675.

Parent, C.A. and Devreotes, P.N. (1996) Molecular genetics of signal transduction in Dictyostelium. Annu Rev Biochem 65, 411-440.

Xiao, Z., Zhang, N., Murphy, D.B. and Devreotes, P.N. (1997) Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation. J. Cell Biol. 139, 365-374.

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 and Development 11, 3218-3231.

Parent, C., Blacklock, B., Froelich, W., Murphy, D. and Devreotes, P.N. (1998) G protein signaling events are activated at the leading edge of chemotactic cells. Cell, 95, 81-91.

Parent, C. and Devreotes, P. (1999) A cell's sense of direction. Science 284, 765-770.

Janetopoulos, C., Jin, T. and Devreotes, P. (2001) Receptor-Mediated Activation of Heterotrimeric G-proteins in Living Cells. Science 291, 2408-2411.

Ueda, M., Sako, Y., Tanaka, T., Devreotes, P., and Yanagida, T. (2001) Single molecule analysis of chemotactic signaling in Dictyostelium cells. Science, 294(5543), 864-7.

Zhao, M., Jin, T., McCaig, C., Forrester, J., and Devreotes, P.N. (2002) Genetic analysis of the role of G protein-coupled receptor signaling in electrotaxis. J. Cell Bio. 157(6), 921-927.

Iijima, M. and Devreotes, P. N. (2002) Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610 (Cover).

Iijima, M., Huang, E., and Devreotes, P.N. (2002) Temporal and spatial regulation of chemotaxis. Dev. Cell 3, 469-478.

Janetopoulos, C. and Deverotes, P.N. 2003 Eukaryotic Chemotaxis: Distinctions between directional sensing and polarization. J. Biol. Chem. 278, 20445-20448.

Luo, H.R., Huang, Y.E., Chen, J.C., Saiardi, A., Iijima, M., Ye, K., Huang, Y., Nagata, E., Devreotes, P.N., and Snyder, S.H. (2003) Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions. Cell 114(5), 559-572.

Janetopoulos, C., Ma, L., Iglesias, P.A., and Devreotes, P.N. (2004) Chemoattractant-induced temporal and spatial PI(3,4,5)P3 accumulation is controlled by a local excitation, global inhibition mechanism. PNAS 101(24):8951-8956.

Iijima, M., Huang, Y.E., Luo, H.R., Vazquez, F., and Devreotes, P.N. (2004) Novel mechanism of PTEN regulation by its Phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis. J. Biol. Chem. 279(16):16606-16613.

Van Haastert, P.J. and Devreotes, P.N. 2004 Chemotaxis: signaling the way forward. Nat. Mol. Cell Biol. 5(8):626-634.

Chen, L., Iijima, M., Tang, M., Landree, M.A., Huang, Y.E., Xiong, Y., Iglesias, P.A., and Devreotes, P.N. (2007) PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev. Cell 12(4):603-614.

Kamimura, Y., Xiong, Y., Iglesias, P.A., Hoeler, O., Bolourani, P. and Devreotes, P.N. 2008 PIP(3)-Independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxis. Curr. Bio. 18:1034-43.

Tang, L., Franca-Koh, J., Xiong, Y., Chen, M-Y., Long, Y., Bickford, R.M., Knecht, D.A., Iglesias, P.A., and Devreotes, P.N. 2007 Tsunami, the Dictyostelium homolog of the Fused kinase is required for polarization and chemotaxis. Genes Dev. 22:2278-2290.

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