Aaron Turkewitz

Research Summary
A network of membrane-bound organelles, interconnected by dynamic vesicular traffic, is a defining hallmark of eukaryotes. Our laboratory studies membrane traffic in the ciliate Tetrahymena thermophila. Our interest in these cells stems from the fact that Tetrahymena is unicellular and offers a host of experimental advantages; the individual cells are remarkably complex and include features that are usually associated with animal cells but absent in fungi. For example, ciliates have a prominent pathway for regulated secretion of polypeptides from specialized vesicles resembling dense core granules. This is in spite of the fact that ciliates are far more distantly related to animals than are most organisms, including yeast, that are commonly studied by cell biologists. We use genetic, cell biological, informatics and biochemical approaches to dissect this and other pathways of membrane trafficking in these remarkable cells.
Keywords
membrane traffic, organelles, regulated exocytosis, evolutionary cell biology, protists, ciliates, lysosome-related organelles
Education
  • Harvard University, Cambridge, MA, Ph.D Biochemistry and Molecular Biology 06/1988
  • UCSF, San Francisco, CA, Cell Biology 06/1992
Publications
  1. Luo GZ, Hao Z, Luo L, Shen M, Sparvoli D, Zheng Y, Zhang Z, Weng X, Chen K, Cui Q, Turkewitz AP, He C. N6-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA. Genome Biol. 2018 11 19; 19(1):200. View in: PubMed

  2. Sparvoli D, Richardson E, Osakada H, Lan X, Iwamoto M, Bowman GR, Kontur C, Bourland WA, Lynn DH, Pritchard JK, Haraguchi T, Dacks JB, Turkewitz AP. Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila. Curr Biol. 2018 03 05; 28(5):697-710.e13. View in: PubMed

  3. de Francisco P, Martín-González A, Turkewitz AP, Gutiérrez JC. Extreme metal adapted, knockout and knockdown strains reveal a coordinated gene expression among different Tetrahymena thermophila metallothionein isoforms. PLoS One. 2017; 12(12):e0189076. View in: PubMed

  4. Tsypin LM, Turkewitz AP. The Co-regulation Data Harvester: automating gene annotation starting from a transcriptome database. SoftwareX. 2017; 6:165-171. View in: PubMed

  5. Kaur H, Sparvoli D, Osakada H, Iwamoto M, Haraguchi T, Turkewitz AP. An endosomal syntaxin and the AP-3 complex are required for formation and maturation of candidate lysosome-related secretory organelles (mucocysts) in Tetrahymena thermophila. Mol Biol Cell. 2017 Jun 01; 28(11):1551-1564. View in: PubMed

  6. Guerrier S, Plattner H, Richardson E, Dacks JB, Turkewitz AP. An evolutionary balance: conservation vs innovation in ciliate membrane trafficking. Traffic. 2017 01; 18(1):18-28. View in: PubMed

  7. Klinger CM, Ramirez-Macias I, Herman EK, Turkewitz AP, Field MC, Dacks JB. Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology. Mol Biochem Parasitol. 2016 Sep - Oct; 209(1-2):88-103. View in: PubMed

  8. Kontur C, Kumar S, Lan X, Pritchard JK, Turkewitz AP. Whole Genome Sequencing Identifies a Novel Factor Required for Secretory Granule Maturation in Tetrahymena thermophila. G3 (Bethesda). 2016 08 09; 6(8):2505-16. View in: PubMed

  9. Kumar S, Briguglio JS, Turkewitz AP. Secretion of Polypeptide Crystals from Tetrahymena thermophila Secretory Organelles (Mucocysts) Depends on Processing by a Cysteine Cathepsin, Cth4p. Eukaryot Cell. 2015 Aug; 14(8):817-33. View in: PubMed

  10. Lynch M, Field MC, Goodson HV, Malik HS, Pereira-Leal JB, Roos DS, Turkewitz AP, Sazer S. Evolutionary cell biology: two origins, one objective. Proc Natl Acad Sci U S A. 2014 Dec 02; 111(48):16990-4. View in: PubMed

  11. Kumar S, Briguglio JS, Turkewitz AP. An aspartyl cathepsin, CTH3, is essential for proprotein processing during secretory granule maturation in Tetrahymena thermophila. Mol Biol Cell. 2014 Aug 15; 25(16):2444-60. View in: PubMed

  12. Briguglio JS, Turkewitz AP. Tetrahymena thermophila: a divergent perspective on membrane traffic. J Exp Zool B Mol Dev Evol. 2014 Nov; 322(7):500-16. View in: PubMed

  13. Amaro F, Turkewitz AP, Martín-González A, Gutiérrez JC. Functional GFP-metallothionein fusion protein from Tetrahymena thermophila: a potential whole-cell biosensor for monitoring heavy metal pollution and a cell model to study metallothionein overproduction effects. Biometals. 2014 Feb; 27(1):195-205. View in: PubMed

  14. Briguglio JS, Kumar S, Turkewitz AP. Lysosomal sorting receptors are essential for secretory granule biogenesis in Tetrahymena. J Cell Biol. 2013 Nov 11; 203(3):537-50. View in: PubMed

  15. Katz LA, Turkewitz AP. Stalking the wild Tetrahymena. Mol Ecol. 2013 Feb; 22(4):912-4. View in: PubMed

  16. Poklepovich TJ, Rinaldi MA, Tomazic ML, Favale NO, Turkewitz AP, Nudel CB, Nusblat AD. The cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants in Saccharomyces cerevisiae. Steroids. 2012 Nov; 77(13):1313-20. View in: PubMed

  17. Nusblat AD, Bright LJ, Turkewitz AP. Conservation and innovation in Tetrahymena membrane traffic: proteins, lipids, and compartments. Methods Cell Biol. 2012; 109:141-75. View in: PubMed

  18. Turkewitz AP, Bright LJ. A Rab-based view of membrane traffic in the ciliate Tetrahymena thermophila. Small GTPases. 2011 Jul; 2(4):222-226. View in: PubMed

  19. Amaro F, Turkewitz AP, Martín-González A, Gutiérrez JC. Whole-cell biosensors for detection of heavy metal ions in environmental samples based on metallothionein promoters from Tetrahymena thermophila. Microb Biotechnol. 2011 Jul; 4(4):513-22. View in: PubMed

  20. Bright LJ, Kambesis N, Nelson SB, Jeong B, Turkewitz AP. Comprehensive analysis reveals dynamic and evolutionary plasticity of Rab GTPases and membrane traffic in Tetrahymena thermophila. PLoS Genet. 2010 Oct 14; 6(10):e1001155. View in: PubMed

  21. Rahaman A, Miao W, Turkewitz AP. Independent transport and sorting of functionally distinct protein families in Tetrahymena thermophila dense core secretory granules. Eukaryot Cell. 2009 Oct; 8(10):1575-83. View in: PubMed

  22. Rahaman A, Elde NC, Turkewitz AP. A dynamin-related protein required for nuclear remodeling in Tetrahymena. Curr Biol. 2008 Aug 26; 18(16):1227-33. View in: PubMed

  23. Elde NC, Long M, Turkewitz AP. A role for convergent evolution in the secretory life of cells. Trends Cell Biol. 2007 Apr; 17(4):157-64. View in: PubMed

  24. Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P, Jones KM, Tallon LJ, Delcher AL, Salzberg SL, Silva JC, Haas BJ, Majoros WH, Farzad M, Carlton JM, Smith RK, Garg J, Pearlman RE, Karrer KM, Sun L, Manning G, Elde NC, Turkewitz AP, Asai DJ, Wilkes DE, Wang Y, Cai H, Collins K, Stewart BA, Lee SR, Wilamowska K, Weinberg Z, Ruzzo WL, Wloga D, Gaertig J, Frankel J, Tsao CC, Gorovsky MA, Keeling PJ, Waller RF, Patron NJ, Cherry JM, Stover NA, Krieger CJ, del Toro C, Ryder HF, Williamson SC, Barbeau RA, Hamilton EP, Orias E. Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biol. 2006 Sep; 4(9):e286. View in: PubMed

  25. Elde NC, Morgan G, Winey M, Sperling L, Turkewitz AP. Elucidation of clathrin-mediated endocytosis in tetrahymena reveals an evolutionarily convergent recruitment of dynamin. PLoS Genet. 2005 Nov; 1(5):e52. View in: PubMed

  26. Bowman GR, Smith DG, Michael Siu KW, Pearlman RE, Turkewitz AP. Genomic and proteomic evidence for a second family of dense core granule cargo proteins in Tetrahymena thermophila. J Eukaryot Microbiol. 2005 Jul-Aug; 52(4):291-7. View in: PubMed

  27. Cowan AT, Bowman GR, Edwards KF, Emerson JJ, Turkewitz AP. Genetic, genomic, and functional analysis of the granule lattice proteins in Tetrahymena secretory granules. Mol Biol Cell. 2005 Sep; 16(9):4046-60. View in: PubMed

  28. Bowman GR, Elde NC, Morgan G, Winey M, Turkewitz AP. Core formation and the acquisition of fusion competence are linked during secretory granule maturation in Tetrahymena. Traffic. 2005 Apr; 6(4):303-23. View in: PubMed

  29. Turkewitz AP. Out with a bang! Tetrahymena as a model system to study secretory granule biogenesis. Traffic. 2004 Feb; 5(2):63-8. View in: PubMed

  30. Haddad A, Bowman GR, Turkewitz AP. New class of cargo protein in Tetrahymena thermophila dense core secretory granules. Eukaryot Cell. 2002 Aug; 1(4):583-93. View in: PubMed

  31. Bradshaw NR, Chilcoat ND, Verbsky JW, Turkewitz AP. Proprotein processing within secretory dense core granules of Tetrahymena thermophila. J Biol Chem. 2003 Feb 07; 278(6):4087-95. View in: PubMed

  32. Fillingham JS, Chilcoat ND, Turkewitz AP, Orias E, Reith M, Pearlman RE. Analysis of expressed sequence tags (ESTs) in the ciliated protozoan Tetrahymena thermophila. J Eukaryot Microbiol. 2002 Mar-Apr; 49(2):99-107. View in: PubMed

  33. Bowman GR, Turkewitz AP. Analysis of a mutant exhibiting conditional sorting to dense core secretory granules in Tetrahymena thermophila. Genetics. 2001 Dec; 159(4):1605-16. View in: PubMed

  34. Turkewitz AP, Orias E, Kapler G. Functional genomics: the coming of age for Tetrahymena thermophila. Trends Genet. 2002 Jan; 18(1):35-40. View in: PubMed

  35. Chilcoat ND, Elde NC, Turkewitz AP. An antisense approach to phenotype-based gene cloning in Tetrahymena. Proc Natl Acad Sci U S A. 2001 Jul 17; 98(15):8709-13. View in: PubMed

  36. Turkewitz AP, Chilcoat ND, Haddad A, Verbsky JW. Regulated protein secretion in Tetrahymena thermophila. Methods Cell Biol. 2000; 62:347-62. View in: PubMed

  37. Verbsky JW, Turkewitz AP. Proteolytic processing and Ca2+-binding activity of dense-core vesicle polypeptides in Tetrahymena. Mol Biol Cell. 1998 Feb; 9(2):497-511. View in: PubMed

  38. Melia SM, Cole ES, Turkewitz AP. Mutational analysis of regulated exocytosis in Tetrahymena. J Cell Sci. 1998 Jan; 111 ( Pt 1):131-40. View in: PubMed

  39. Chilcoat ND, Turkewitz AP. In vivo analysis of the major exocytosis-sensitive phosphoprotein in Tetrahymena. J Cell Biol. 1997 Dec 01; 139(5):1197-207. View in: PubMed

  40. Haddad A, Turkewitz AP. Analysis of exocytosis mutants indicates close coupling between regulated secretion and transcription activation in Tetrahymena. Proc Natl Acad Sci U S A. 1997 Sep 30; 94(20):10675-80. View in: PubMed

  41. Chilcoat ND, Melia SM, Haddad A, Turkewitz AP. Granule lattice protein 1 (Grl1p), an acidic, calcium-binding protein in Tetrahymena thermophila dense-core secretory granules, influences granule size, shape, content organization, and release but not protein sorting or condensation. J Cell Biol. 1996 Dec; 135(6 Pt 2):1775-87. View in: PubMed

  42. Turkewitz AP, Sullivan CP, Mescher MF. Large-scale purification of murine I-Ak and I-Ek antigens and characterization of the purified proteins. Mol Immunol. 1983 Nov; 20(11):1139-47. View in: PubMed

  43. Mescher MF, Stallcup KC, Sullivan CP, Turkewitz AP, Herrmann SH. Purification of murine MHC antigens by monoclonal antibody affinity chromatography. Methods Enzymol. 1983; 92:86-109. View in: PubMed

  44. Turkewitz AP, Amatruda JF, Borhani D, Harrison SC, Schwartz AL. A high yield purification of the human transferrin receptor and properties of its major extracellular fragment. J Biol Chem. 1988 Jun 15; 263(17):8318-25. View in: PubMed

  45. Turkewitz AP, Schwartz AL, Harrison SC. A pH-dependent reversible conformational transition of the human transferrin receptor leads to self-association. J Biol Chem. 1988 Nov 05; 263(31):16309-15. View in: PubMed

  46. Schwartz AL, Ciechanover A, Merritt S, Turkewitz A. Antibody-induced receptor loss. Different fates for asialoglycoproteins and the asialoglycoprotein receptor in HepG2 cells. J Biol Chem. 1986 Nov 15; 261(32):15225-32. View in: PubMed

  47. Turkewitz AP, Harrison SC. Concentration of transferrin receptor in human placental coated vesicles. J Cell Biol. 1989 Jun; 108(6):2127-35. View in: PubMed

  48. Turkewitz AP, Madeddu L, Kelly RB. Maturation of dense core granules in wild type and mutant Tetrahymena thermophila. EMBO J. 1991 Aug; 10(8):1979-87. View in: PubMed

  49. Turkewitz AP, Kelly RB. Immunocytochemical analysis of secretion mutants of Tetrahymena using a mucocyst-specific monoclonal antibody. Dev Genet. 1992; 13(2):151-9. View in: PubMed