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Primary Faculty
Peter N. Devreotes, Ph.D.
The Isaac Morris and Lucille Elizabeth Hay Professor
Director, Department of Cell Biology
Johns Hopkins University School of Medicine
725 N. Wolfe St., 114 WBSB
Baltimore, MD 21205
   
Telephone: 410-955-3225 (Office)
410-955-4699 (Lab)
Fax: 410-614-9461
Email: pnd@jhmi.edu
Website: http://www.hopkinsmedicine.org/cellbio/devreotes/
Assistant: Pam Antol
410-502-6810
pjantol@jhmi.edu

 

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.
Select Publications

Rahdar, M., Inoue, T., Meyer T., Zhang, J., Vazquez, F., Devreotes, P.N.  2008  A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN.  PNAS 2009;106:480-485.

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.  2008 Tsunami, the Dictyostelium homolog of the Fused kinase is required for polarization and chemotaxis.  Genes Dev. 22:2278-2290.

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.

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.

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

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.

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.

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

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

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

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.

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.

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

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

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.

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.

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.

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.

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

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.

 

 

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