Peter N. Devreotes, Ph.D.

Isaac Morris & Lucille Elizabeth Hay Professor Director Emeritus, Department of Cell Biology Distinguished Service Professor, Johns Hopkins University

410-955-3225 (Office), 410-955-4699 (Lab), 410-614-9461 (Fax)

Johns Hopkins University School of Medicine
725 N. Wolfe St., 114 WBSB
Baltimore, MD 21205

Website

Academic Titles

Professor

Research Topic

Genetic analysis of chemotaxis in eukaryotic cells

Research Topic:  Genetic analysis of chemotaxis in eukaryotic cells

Many cells have an internal “compass” that allows them to detect and move along extracellular chemical gradients in a process referred to as chemotaxis or directed cell migration. In embryogenesis, chemotaxis is used repeatedly to rearrange cells, for instance, during primordial germ cell migration, organ formation, and wiring of the nervous system. In the adult, chemotaxis mediates normal trafficking of immune cells and is critical for inflammation. It also participates in wound healing, in maintenance of tissue architecture, and allows stem cells to target to and persist in their niches.

Chemotaxis bias depends on a network composed of multiple signaling pathways. Several years ago, we discovered that chemoattractants activate PI3Ks producing an accumulation of PIP3 at the leading edge of amoebae. We now know that this mechanism is conserved in neutrophils and many other types of eukaryotic cells. Unregulated production of PIP3, as occurs in cells lacking the tumor suppressor PTEN, causes many ectopic projections and impairs the directional response of migrating cells. Thus, localized PIP3 production is an important conserved mechanism mediating chemotactic bias. However, additional pathways act in parallel or redundantly with PIP3.

In our search for parallel pathways, we have found that TorC2 is activated at the leading edge of the cell and causes the localized activation of PKBs and phosphorylation of PKB substrates. The absence of these phosphorylation events in cells lacking PiaA leads to a defect in chemotaxis. This pathway acts in parallel with PIP3 to mediate the chemotactic response. It has recently been found that the TorC2 mechanism is conserved in chemotaxing neutrophils. Most recently, using TIRF, we have found that signaling events propagate in waves along the basal surface of the cell.  We are investigating how these spontaneous signaling waves coordinate the activity of the cytoskeleton to make cellular protrusions.

Our long term goal is acomplete description of the network controlling chemotactic behavior. We are analyzing combinations of deficiencies to understand interactions among network components and carrying out additional genetic screens to identify new pathways involved in chemotaxis. A comprehensive understanding of this fascinating process should lead to control of pathological conditions such as inflammation and cancer metastasis.

Devreotes-New Biosketch_10-08-2021

Research Associates and Staff

Name Position Title Email Phone
Brigitte Walsh Assistant bwalsh12@jhmi.edu 410-502-6810

Lab Members

Name Classification Email Phone
Bedri Abubeker-Sharif Student bedri@jhmi.edu 410-955-4699
Chris Janetopoulos, Ph.D. Visiting Scientist cjaneto1@jh.edu 410-955-4699
Dhiman Pal, Ph.D. Postdoctoral Fellow dpal1@jhmi.edu 410-502-6810
Huiwang (David) Zhan, Ph.D. Postdoctoral Fellow huiwangzhan@jhmi.edu 410-955-4699
Jane Borleis Research Specialist jborleis@jhmi.edu 410-955-4699
Jonathan Kuhn, Ph.D. Postdoctoral Fellow jkuhn14@jhmi.edu 410-955-4699
Suchitra Mitra, Ph.D. Postdoctoral Fellow 410-955-4699
Tatsat Banerjee Student tatsatb@jhu.edu 410-955-4699
Wei Qian Research Technologist wqian1@jhmi.edu 410-955-3225
Yiyan Lin Student ylin123@jhmi.edu 410-955-4699
Yu Deng Student ydeng25@jhu.edu 410-955-4699
Yu Long Research Specialist yulong@jhmi.edu 410-955-4699

Publications

  • Pal DS, Banerjee T, Lin Y, Borleis J and Devreotes PN. 2022. Direct activation of the Ras-Akt network mediates polarity and organizes protrusions in human neutrophil migration. bioRxiv 10-28-22. https://www.biorxiv.org/content/10.1101/2022.10.27.513966v1 (preprint).
  • Yang Q, Miao Y, Banerjee P, Hourwitz MJ, Hu M, Qing Q, Iglesias PA, Devreotes PN, Fourkas JG and Losert W. 2022. Nanotopography modulates intracellular excitable systems through cytoskeleton actuation. bioRxiv June 9, 2022.  https://doi.org/10.1101/2022.06.09.495528 (preprint).
  • Banerjee T, Biswas D*, Pal DS*, Miao Y, Iglesias PA and Devreotes PN. 2022. Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration. Nat Cell Biol. 2022 Oct 6. Online ahead of print. doi: 10.1038/s41556-022-00997-7. *Co-second Authors
  • Yang Q, Miao Y, Campanello LJ, Hourwitz MJ, Bull AL, Devreotes PN, FourkasJT and Losert W. 2022. Cortical waves mediate the cellular response to electric fields. Elife. 2022 Mar 23;11:e73198. doi: 10.7554/eLife.73198. PMC8942472.
  • Ghabache E, Cao Y, Miao Y, Groisman A, Devreotes PN and Rappel W-J. 2021. Coupling traction force patterns and actomyosin wave dynamics reveals mechanics of cell motion. Mol Sys Biol. 2021;17:e10505. doi: 10.15252/msb.202110505.
  • Kuhn J, Lin Y and Devreotes PN. 2021. Using live-cell imaging and synthetic biology to probe directed migration in Dictyostelium. Front. Cell Dev Biol. 2021 Oct 05. doi: 10.3389/fcell.2021.740205.
  • Biswas D, Devreotes PN and Iglesias PA. 2021. Three-dimensional stochastic simulation of chemoattractant-mediated excitability in cells. PLoS Comput Biol. 2021 Jul 14;17(7):e1008803. PMC8330952. doi: 10.1371/journal.pcbi.1008803. eCollection 2021 Jul.
  • Song B, Gu Y, Jiang W, Li Y, Ayre WN, Liu Z, Yin T, Janetopoulos C, Iijima M, Devreotes P, Zhao M. 2021. Electric signals counterbalanced posterior vs. anterior PTEN signaling in directed cell migration of Dictyostelium. Cell Biosci. 2021 Jun 14;11(1):111. PMC8201722.
  • Kim JH, Hanlon CD, Vohra S, Devreotes PN and Andrew DJ. 2021. Hedgehog signaling and Tre1 regulate actin dynamics through PI(4,5)P2 to direct migration of Drosophila embryonic germ cells. Cell Rep. 2021 Mar 2;34(9):108799.  doi: 10.1016/j.celrep.2021.108799. PMC8023404.
  • Li X, Pal DS, Biswas D, Iglesias PA and Devreotes PN. Reverse fountain flow of phospha-tidylinositol-3,4- biphosphate polarizes migrating cells. EMBO J. 2021 Feb 15;40(4):e105094. doi: 10.15252/embj.2020105094.
  • Zhan H, Bhattacharya S, Cai H, Iglesias PA, Huang C-H, Devreotes PN. 2020. An Excitable Ras/PI3K/ERK Signaling Network Controls Migration and Oncogenic Transformation in Epithelial Cells. Dev Cell. 2020 Aug 31;S1534-5807(20)30599-2. doi: 10.1016/j.devcel.2020.08.001.
  • Bhattacharya S, Banerjee T, Miao Y, Zhan H, Devreotes PN, Iglesias PA. 2020. Traveling and standing waves mediate pattern formation in cellular protrusions.  Science Advances. 2020 Aug 7; 6(32): eaay 7682. doi: 10.1126/sciadv.aay7682.

  • Jiao Z, Cai H, Long Y, Sirka OK, Padmanaban V, Ewald AJ, Devreotes PN (2020). Statin-induced GGPP depletion blocks macropinocytosis and starves cells with oncogenic defects. Proc Natl Acad Sci U S A, 117(8), 4158-4168. doi: 10.1073/pnas.1917938117.

  • Cao Y, Ghabache E, Miao Y, Niman C, Hakozaki H, Reck-Peterson SL, Devreotes PN, and Rappel W-J.  2019. A minimal computational model for three-dimensional cell migration. J. R. Soc. Interface 16:20190619. http://dx.doi.org/10.1098/rsif.2019.0619

  • Pal DS*, Li X*, Banerjee T, Miao Y, Devreotes PN. 2019. The Excitable Signal Transduction Networks: Movers and Shapers of Eukaryotic Cell Migration. Int. J. Dev. Biol. 63(8-9-10):407-416. doi: 10.1387/ijdb.190265pd. *Equal contribution.

  • Li X, Miao Y, Pal DS, Devreotes PN. Excitable networks controlling cell migration during development and disease. Semin Cell Dev Biol. 2019 Dec 10;. doi: 10.1016/j.semcdb.2019.11.001. [Epub ahead of print] Review. PubMed PMID: 31836289; NIHMSID:NIHMS1546309

  • Devreotes P (2019). Moving toward molecular mechanisms for chemotaxis in eukaryotic cells. Mol Biol Cell, 30(23), 2873-2877, 2019 Nov 1. doi: 10.1091/mbc.E19-07-0393. PMC6822590.

  • Miao Y, Battacharya S, Banerjee T, Abudaker-Sharif B, Long Y, Inoue T, Iglesias P and Devreotes P. (2019). Wave patterns organize cellular protrusions and control cortical dynamics. Molecular Systems Biology 15(3). DOI 10.15252/msb.20188585| Published online 11.03.2019.

  • Miyanaga Y, Kamimura Y, Kuwayama H, Devreotes PN, and Ueda M. (2018). Chemoattractant receptors activate, recruit and capture G proteins for wide range chemotaxis. Biochemical and Biophysical Research Communications. Nov 16. pii: S0006-291X(18)32435-5. doi: 10.1016/j.bbrc.2018.11.029. [Epub ahead of print] PubMed PMID: 30454895.

  • Li X, Edwards M, Swaney KF, Singh N, Bhattacharya S, Borleis J, Long Y, Iglesias PA, Chen J, and Devreotes PN. 2018. Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration. PNAS published ahead of print Sept. 7, 2018. https://doi.org/10.1073/pnas.1809039115

  • Edwards M, Cai H, Abubaker-Sharif  B, Long Y, Lampert T, and Devreotes PN. 2018. Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum. Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3722-E3730. doi: 10.1073/pnas.1710480115. Epub 2018 Mar 30.

  • Neumann NM, Perrone MC, Veldhuis JH, Huebner RJ, Zhan H, Devreotes PN, Brodland GW, and Ewald AJ. 2018. Coordination of receptor tyrosine kinase signaling and interfacial tension dynamics drives radial intercalation and tube elongation. Dev Cell Apr 9;45(1):67-82.e6. doi: 10.1016/j.devcel.2018.03.11.

  • Artemenko, Y., Devreotes, P. N. Assessment of Dictyostelium discoideum Response to Acute Mechanical Stimulation. J. Vis. Exp.(129), e56411, doi:10.3791/56411 (2017).

  • Devreotes PN, Bhattacharya S, Edwards M, Iglesias PA, Lampert T, Miao Y. 2017. Excitable Signal Transduction Networks in Directed Cell Migration. Annu Rev Cell Dev Biol Oct. 6;33:103-125. Doi: 10.1146/annurev-cellbio-100616-060739. PMID: 28793794

  • Lampert TJ, Kamprad N, Edwards M, Borleis J, Watson AJ, Tarantola M, Devreotes PN.  2017. Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity. Proc Natl Acad Sci USA Aug 28. Pii: 201616600. Doi: 10.1073/pnas.1616600114. [Epub ahead of print]. PMCID: PMC5603988

  • Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel M, Gabelli SB, Cole PA.  2017. A Tunable Brake for HECT Ubiquitin Ligases. Molecular Cell 66 (3): 345-357. PMID: 28475870. DOI: 10.1016/j.molcel.2017.03.020

  • Miao Y, Bhattacharya S, Edwards M, Cai H, Inoue T, Iglesias P, Devreotes PN. 2017.  Altering the threshold of an excitable signal transduction network changes cell migratory modes.  Nat Cell Biol 19:329-340.

  • Artemenko Y, Axiotakis L Jr., Borleis J, Iglesias PA, Deveotes PN. 2016. Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks. Proc Natl Acad Sci USA. Nov. 22; 113(47):E7500-E7509. PMCID: PMC5127353 https://www.ncbi.nlm.nih.gov/pubmed/27821730

  • Swaney K.F., Borleis J., Iglesias P.A., and Devreotes, P.N. 2015.  Novel protein Callipygian defines the back of migrating cells. PNAS 2015 Jun 30. pii:201509098. [Epub ahead of print]

  • Tang M, Wang M, Shi C, Iglesias PA, Devreotes PN, and Huang CH  (2014).  Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis. Nat Commun. Oct 27;5:5175. PMCID: PMC4211273 [Available on 2015/4/27)]

  • Cai H, Katoh-Kurasawa M, Muramoto T, Santhanam B, Long Y, Li L, Ueda M, Iglesias PA, Shaulsky G, and Devreotes PN. Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer. Science. 2014 Mar 21;343(6177):1249531. doi: 10.1126/science.1249531.

  • Huang, C.,Tang, M., Shi, C., Iglesias, P., and Devreotes, P.N. An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat Cell Biol. 2013 Nov;15(11):1307-16.

  • Shi, C., Huang, C., Devreotes, P.N., and Iglesias, P.  2013. Interaction of motility, directional sensing, and polarity modules recreates the behaviors of chemotaxing cells. PLOS Computational Biol. 2013 Jul;9(7):e1003122. 

  • Cai, H., Das, S., Kamimura, Y., Comer, F.I., Parent, D.A., and Devreotes, P.N.  2010  Ras-mediated activation and inactivation of the TorC2-PKB pathway are critical for chemotaxis.  J. Cell Biol., 190:233-245. PMCID: PMC2930282

  • Xiong, Y., Huang, C-H, Iglesias, P.A., and Devreotes, P.N. 2010. Cells navigate with a local-excitation, global-inhibition-biased excitable network. PNAS, 107:17079-17086.

  • Swaney, K.F., Huang, C.H., Devreotes, P.N. 2010. Eukaryotic Chemotaxis: A network of signaling pathways controls motility, directional sensing, and polarity. Annu Rev Biophys 278:20445-20448.

  • Janetopoulos C, Ma L, Devreotes PN, Iglesias PA. Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8951-6. PMC428453. 

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

  • Janetopoulos, C., Jin, T. and Devreotes, P.N. 2001. Receptor mediated activation of heterotrimeric G-proteins in living cells. Science, 291, 2408-2411.

  • Parent, C. and Devreotes, P.N. 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 MY, Long Y, Devreotes PN. A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium. Genes Dev. 1997 Dec 1;11(23):3218-31. PMC316743. 

  • Xiao Z, Zhang N, Murphy DB, Devreotes PN. Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation. J Cell Biol. 1997 Oct 20;139(2):365-74. PMC2139806.

  • Insall R, Kuspa A, Lilly PJ, Shaulsky G, Levin LR, Loomis WF, Devreotes P. CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium. J Cell Biol. 1994 Sep;126(6):1537-45. PMC2290948. 

  • Lilly P, Wu L, Welker DL, Devreotes PN. A G-protein beta-subunit is essential for Dictyostelium development. Genes Dev. 1993 Jun;7(6):986-95. PMID: 8099335.

  • Pitt, G.S., Milona, N., Borleis, J., Lin, K.C., Reed, R.R. and Devreotes, P.N. 1992. Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyosteilum development. Cell 69, 305-315.

  • Klein, P.S., Sun, T.L., Saxe, C.L. III, Kimmel, A.R., Johnson, R.L. and Devreotes, P.N.  1988.  A chemoattractant receptor controls development in Dictyostelium discoideum. Science 241, 1467-1472.

  • Tomchik KJ, Devreotes PN. Adenosine 3',5'-monophosphate waves in Dictyostelium discoideum: a demonstration by isotope dilution--fluorography. Science. 1981 Apr 24;212(4493):443-6. (Cover Article). PMID: 6259734. 

  • Devreotes PN, Steck TL. Cyclic 3',5' AMP relay in Dictyostelium discoideum. II. Requirements for the initiation and termination of the response. J Cell Biol. 1979 Feb;80(2):300-9. PMC2110342.