|Rank||Professor and Director|
|School of Medicine Address||JHU School of Medicine|
725 N. Wolfe St., 114 WBSB
Baltimore MD 21205
|Link to Lab Homepage|
Research Topic: Genetic analysis of chemotaxis eukaryotic cells
Chemotaxis plays a key role in immune response, wound healing, angiogenesis, and embryogenesis as well as mediating cancer metastasis. Research in Dictyostelium discoideum has shown that chemoattractants are sensed by GPCRs 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 and epithelial cells. We found that cell motility depends on spontaneous activation of the signal transduction network and that directional cues bias the threshold for activation. Numerous signal transduction events are activated or inactivated on each pseudopod. For example, activation of PI3K and inactivation of PTEN leads to a local accumulation of PIP3. Activation of protein kinases B requires both PIP3 and 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 pathways.
Swaney K.F., Borleis J., Iglesias P.A., and Devreotes, P.N
. 2015. Novel protein Callipygian defines the back of migrating cells. Proc Natl Acad Sci U S A. Jun 30. Pii:201509098 [Epub ahead of print]. PMID: 26130809.PubMed Reference
Cai H, Katoh-Kurasawa M., Muramoto T, Santhanam B, Long Y, Li L, Ueda M, Iglesias PA, Shaulsky G, and Devreotes PN. 2013. Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer. Science. 2014 Mar 21;343(6177):1249531. Doi: 10.1126/science.1249531. PMCID: PMC Journal
Huang C,Tang M, Shi C, Iglesias P, and Devreotes PN
. An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat Cell Biol. 2013 Nov;15(11):1307-16.
Nguyen HN, Afkari Y, Senoo H, Sesaki H, Devreotes PN
, and Iijima M. Mechanisms of human PTEN localization revealed by heterologous expression in Dictyostelium. Oncogene, in press.
Tang M, Iijima M, and Devreotes PN
. 2011. Generation of cells that ignore the effects of PIP3 on cytoskeleton. Cell Cycle, 10:2817-2818.
Tang M, Iijima M, Kamimura Y, Chen L, Long Y, and Devreotes PN
. 2011 Disruption of PKB signaling restores polarity to cells lacking tumor suppressor PTEN. Mol. Biol. Cell. 22:437-447.
Swaney KF, Huang CH, Devreotes PN.
2010 Eukaryotic Chemotaxis: A network of signaling pathways controls motility, directional sensing, and polarity. Annu Rev Biophys 278:20445-20448.
Xiong Y, Huang CH, Iglesias PA., and Devreotes PN
. 2010 Cells navigate with a local-excitation, global-inhibition-biased excitable network. PNAS, 107:17079-17086.
Rahdar M, Inoue T, Meyer T, Zhang J, Vazquez F, Devreotes PN
. 2008 A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN. PNAS 106:480-485.
Chen L, Iijima M, Tang M, Landree MA, Huang YE, Xiong Y, Iglesias PA, and Devreotes PN
. 2007 PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev. Cell 12(4):603-614.
Janetopoulos C, Borleis J, Vazquez F, Iijima M, and Devreotes PN.
2005 Temporal and spatial regulation of phosphoinositide signaling mediates cytokinesis. Dev. Cell 8:467-477.
Iijima M, Huang YE, Luo HR, Vazquez F, and Devreotes PN.
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.
Luo, HR, Huang YE, Chen JC, Saiardi A, Iijima M, Ye K, Huang Y, Nagata E, Devreotes PN
, and Snyder SH. 2003 Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions. Cell 114(5), 559-572.
Iijima M, Huang E, and Devreotes PN
. 2002 Temporal and spatial regulation of chemotaxis. Dev. Cell 3, 469-478.
Janetopoulos C, Jin T and Devreotes PN. 2001. Receptor mediated activation of heterotrimeric G-proteins in living cells. Science, 291, 2408-2411.
Parent C. and Devreotes PN. 1999. A Cell's Sense of Direction. Science, 284, 765-770.
Parent C, Blacklock B, Froelich W, Murphy D and Devreotes PN. 1998. G protein signaling events are activated at the leading edge of chemotactic cells. Cell, 95, 81-91.
Pitt GS, Milona N, Borleis J, Lin KC, Reed RR and Devreotes PN. 1992. Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyosteilum development. Cell 69, 305-315.
Klein PS, Sun TL. Saxe CL III, Kimmel AR, Johnson RL and Devreotes PN. 1988. A chemoattractant receptor controls development in Dictyostelium discoideum. Science 241, 1467-1472.
Tomchik KJ and Devreotes PN. 1981. Cyclic AMP waves in Dictyostelium discoideum: A demonstration by isotope dilution fluorography. Science 212, 443-446.