Research Summary
PI last name in publications: ARAÇ ARAÇ LAB RESEARCH Cells in multicellular organisms have the extraordinary ability of adhering to each other and exchanging information. Cellular adhesion and communication is essential for the development of all organs such as the brain, and is a key phenomenon that is disrupted in many human diseases. The Araç Lab is interested in understanding cellular communication with a special focus on the cell-surface receptors that mediate intercellular adhesion and communication. Genetic studies revealed critical roles for these surface proteins in embryonic development (especially of the brain and the heart), and in neurobiology (especially in synaptogenesis, axon pathfinding, axon-dendrite partner marching and wiring the brain); and link them to numerous diseases including neurological disorders, developmental impairments, multiple types of cancers (such as glioblastoma and ovarian cancer) and congenital general anosmia (the inability to smell). Considering that many drugs target the extracellular regions of membrane receptors to regulate receptor function, and have excellent therapeutic benefits, these proteins may be promising targets for drugs to treat numerous diseases once mechanistic details about the components that regulate their functions are understood. However, in spite of the recent exciting advances, their mechanisms of action, high-resolution structures in isolation or in complex with their ligands, and how they can mediate such broad range of functions remain majorly unknown. Our lab’s ultimate goal is to understand the mechanisms by which cell-adhesion receptors mediate communication between cells.
Keywords
Brain, structural biology, Electron Microscopy, Crystallography, X Ray, multicellularity, Cell Surface Proteins, Membrane Proteins, G Protein Coupled Receptors, Signaling Pathways, Synapses, cortex development, Myelination, Neurobiology, Molecular
Education
  • Stanford University, Stanford, CA, Postdoctoral Structural and Cellular Biology 2013
  • UT Southwestern Med. Center, Dallas, TX, PhD Molecular Biophysics 2006
  • Bilkent University, Ankara, Turkey , BS Molecular Biology and Genetics 1999
Biosciences Graduate Program Association
Awards & Honors
  • 1999 - 2000 Chancellor’s Distinguished Fellowship University of California, Riverside
  • 2007 - 2010 Life Sciences Research Foundation Postdoctoral Fellowship Howard Hughes Medical Center
  • 2014 - 2015 Big Ideas Generator University of Chicago
  • 2014 - 2015 Fay/Frank Seed Grant Brain Research Foundation
Publications
  1. Araç D, Li J. Teneurins and latrophilins: two giants meet at the synapse. Curr Opin Struct Biol. 2019 02; 54:141-151. View in: PubMed

  2. Nazarko O, Kibrom A, Winkler J, Leon K, Stoveken H, Salzman G, Merdas K, Lu Y, Narkhede P, Tall G, Prömel S, Araç D. A Comprehensive Mutagenesis Screen of the Adhesion GPCR Latrophilin-1/ADGRL1. iScience. 2018 May 25; 3:264-278. View in: PubMed

  3. Skubák P, Araç D, Bowler MW, Correia AR, Hoelz A, Larsen S, Leonard GA, McCarthy AA, McSweeney S, Mueller-Dieckmann C, Otten H, Salzman G, Pannu NS. A new MR-SAD algorithm for the automatic building of protein models from low-resolution X-ray data and a poor starting model. IUCrJ. 2018 Mar 01; 5(Pt 2):166-171. View in: PubMed

  4. Li J, Shalev-Benami M, Sando R, Jiang X, Kibrom A, Wang J, Leon K, Katanski C, Nazarko O, Lu YC, Südhof TC, Skiniotis G, Araç D. Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse. Cell. 2018 04 19; 173(3):735-748.e15. View in: PubMed

  5. Salzman GS, Zhang S, Gupta A, Koide A, Koide S, Araç D. Stachel-independent modulation of GPR56/ADGRG1 signaling by synthetic ligands directed to its extracellular region. Proc Natl Acad Sci U S A. 2017 09 19; 114(38):10095-10100. View in: PubMed

  6. Araç D, Sträter N, Seiradake E. Understanding the Structural Basis of Adhesion GPCR Functions. Handb Exp Pharmacol. 2016; 234:67-82. View in: PubMed

  7. Salzman GS, Ackerman SD, Ding C, Koide A, Leon K, Luo R, Stoveken HM, Fernandez CG, Tall GG, Piao X, Monk KR, Koide S, Araç D. Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains. Neuron. 2016 Sep 21; 91(6):1292-1304. View in: PubMed

  8. Lu YC, Nazarko OV, Sando R, Salzman GS, Li NS, Südhof TC, Araç D. Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion. Structure. 2015 Sep 01; 23(9):1678-1691. View in: PubMed

  9. Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev. 2015; 67(2):338-67. View in: PubMed

  10. Liebscher I, Ackley B, Araç D, Ariestanti DM, Aust G, Bae BI, Bista BR, Bridges JP, Duman JG, Engel FB, Giera S, Goffinet AM, Hall RA, Hamann J, Hartmann N, Lin HH, Liu M, Luo R, Mogha A, Monk KR, Peeters MC, Prömel S, Ressl S, Schiöth HB, Sigoillot SM, Song H, Talbot WS, Tall GG, White JP, Wolfrum U, Xu L, Piao X. New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors. Ann N Y Acad Sci. 2014 Dec; 1333:43-64. View in: PubMed

  11. Tsetsenis T, Boucard AA, Araç D, Brunger AT, Südhof TC. Direct visualization of trans-synaptic neurexin-neuroligin interactions during synapse formation. J Neurosci. 2014 Nov 05; 34(45):15083-96. View in: PubMed

  12. Luo R, Jeong SJ, Yang A, Wen M, Saslowsky DE, Lencer WI, Araç D, Piao X. Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation. PLoS One. 2014; 9(6):e100043. View in: PubMed

  13. Prömel S, Langenhan T, Araç D. Matching structure with function: the GAIN domain of adhesion-GPCR and PKD1-like proteins. Trends Pharmacol Sci. 2013 Aug; 34(8):470-8. View in: PubMed

  14. Araç D, Aust G, Calebiro D, Engel FB, Formstone C, Goffinet A, Hamann J, Kittel RJ, Liebscher I, Lin HH, Monk KR, Petrenko A, Piao X, Prömel S, Schiöth HB, Schwartz TW, Stacey M, Ushkaryov YA, Wobus M, Wolfrum U, Xu L, Langenhan T. Dissecting signaling and functions of adhesion G protein-coupled receptors. Ann N Y Acad Sci. 2012 Dec; 1276:1-25. View in: PubMed

  15. Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT. A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J. 2012 Mar 21; 31(6):1364-78. View in: PubMed

  16. Zhang C, Atasoy D, Araç D, Yang X, Fucillo MV, Robison AJ, Ko J, Brunger AT, Südhof TC. Neurexins physically and functionally interact with GABA(A) receptors. Neuron. 2010 May 13; 66(3):403-16. View in: PubMed

  17. Ko J, Zhang C, Arac D, Boucard AA, Brunger AT, Südhof TC. Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation. EMBO J. 2009 Oct 21; 28(20):3244-55. View in: PubMed

  18. Zuniga JE, Schmidt JJ, Fenn T, Burnett JC, Araç D, Gussio R, Stafford RG, Badie SS, Bavari S, Brunger AT. A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate. Structure. 2008 Oct 08; 16(10):1588-97. View in: PubMed

  19. Araç D, Boucard AA, Ozkan E, Strop P, Newell E, Südhof TC, Brunger AT. Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions. Neuron. 2007 Dec 20; 56(6):992-1003. View in: PubMed

  20. Dai H, Shen N, Araç D, Rizo J. A quaternary SNARE-synaptotagmin-Ca2+-phospholipid complex in neurotransmitter release. J Mol Biol. 2007 Mar 30; 367(3):848-63. View in: PubMed

  21. Rizo J, Chen X, Araç D. Unraveling the mechanisms of synaptotagmin and SNARE function in neurotransmitter release. Trends Cell Biol. 2006 Jul; 16(7):339-50. View in: PubMed

  22. Li L, Shin OH, Rhee JS, Araç D, Rah JC, Rizo J, Südhof T, Rosenmund C. Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. J Biol Chem. 2006 Jun 09; 281(23):15845-52. View in: PubMed

  23. Araç D, Chen X, Khant HA, Ubach J, Ludtke SJ, Kikkawa M, Johnson AE, Chiu W, Südhof TC, Rizo J. Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids. Nat Struct Mol Biol. 2006 Mar; 13(3):209-17. View in: PubMed

  24. Chen X, Araç D, Wang TM, Gilpin CJ, Zimmerberg J, Rizo J. SNARE-mediated lipid mixing depends on the physical state of the vesicles. Biophys J. 2006 Mar 15; 90(6):2062-74. View in: PubMed

  25. Ferguson AD, Labunskyy VM, Fomenko DE, Araç D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J. NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. J Biol Chem. 2006 Feb 10; 281(6):3536-43. View in: PubMed

  26. Araç D, Dulubova I, Pei J, Huryeva I, Grishin NV, Rizo J. Three-dimensional structure of the rSly1 N-terminal domain reveals a conformational change induced by binding to syntaxin 5. J Mol Biol. 2005 Feb 18; 346(2):589-601. View in: PubMed

  27. Jarousse N, Wilson JD, Arac D, Rizo J, Kelly RB. Endocytosis of synaptotagmin 1 is mediated by a novel, tryptophan-containing motif. Traffic. 2003 Jul; 4(7):468-78. View in: PubMed

  28. Araç D, Murphy T, Rizo J. Facile detection of protein-protein interactions by one-dimensional NMR spectroscopy. Biochemistry. 2003 Mar 18; 42(10):2774-80. View in: PubMed

  29. Dulubova I, Yamaguchi T, Arac D, Li H, Huryeva I, Min SW, Rizo J, Sudhof TC. Convergence and divergence in the mechanism of SNARE binding by Sec1/Munc18-like proteins. Proc Natl Acad Sci U S A. 2003 Jan 07; 100(1):32-7. View in: PubMed

  30. Kulik V, Weyand M, Seidel R, Niks D, Arac D, Dunn MF, Schlichting I. On the role of alphaThr183 in the allosteric regulation and catalytic mechanism of tryptophan synthase. J Mol Biol. 2002 Dec 06; 324(4):677-90. View in: PubMed

  31. Hafezparast M, Ball S, Nicholson SJ, Witherden A, Arac D, Broadway N, Saggerson D, Cooper E, Naase M, Gokhale S, Quant P, Lascelles C, Nickols C, Baker CS, Peters J, Martin JE, Fisher EM. A new mouse mutant, skijumper. Mamm Genome. 2002 Jul; 13(7):359-364. View in: PubMed

  32. Antonin W, Dulubova I, Arac D, Pabst S, Plitzner J, Rizo J, Jahn R. The N-terminal domains of syntaxin 7 and vti1b form three-helix bundles that differ in their ability to regulate SNARE complex assembly. J Biol Chem. 2002 Sep 27; 277(39):36449-56. View in: PubMed

  33. Witherden AS, Hafezparast M, Nicholson SJ, Ahmad-Annuar A, Bermingham N, Arac D, Rankin J, Iravani M, Ball S, Peters J, Martin JE, Huntley D, Hummerich H, Sergot M, Fisher EM. An integrated genetic, radiation hybrid, physical and transcription map of a region of distal mouse chromosome 12, including an imprinted locus and the 'Legs at odd angles' (Loa) mutation. Gene. 2002 Jan 23; 283(1-2):71-82. View in: PubMed

  34. Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J. Three-dimensional structure of the complexin/SNARE complex. Neuron. 2002 Jan 31; 33(3):397-409. View in: PubMed

  35. Fernandez I, Araç D, Ubach J, Gerber SH, Shin O, Gao Y, Anderson RG, Südhof TC, Rizo J. Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine. Neuron. 2001 Dec 20; 32(6):1057-69. View in: PubMed

  36. Ubach J, Lao Y, Fernandez I, Arac D, Südhof TC, Rizo J. The C2B domain of synaptotagmin I is a Ca2+-binding module. Biochemistry. 2001 May 22; 40(20):5854-60. View in: PubMed