Research Summary

Our laboratory studies membrane traffic in a somewhat exotic model system, the ciliate Tetrahymena thermophila. Ciliates emerged as an early branch during eukaryotic evolution, and are far more distantly related to humans, for example, than are most organisms being studied by cell biologists. Our interest in these cells stems from the fact that ciliates are unicellular and offer a host of experimental advantages, but at the same time are highly complex and maintain many cellular features that are usually associated with animal cells. In particular, ciliates have a prominent pathway for regulated secretion of polypeptides via dense core granules. Such granules arise by mechanisms that are poorly understood in the mammalian cells in which they have classically been studied. We use a combination of biochemical and genetic approaches, taking advantage of the ability to derive viable Tetrahymena mutants with defects in granule function. Our second major interest is in the "opposite" process, endocytosis, by which membrane is taken up from the cell surface. Ciliates also appear to maintain endocytic structures that are remarkably similar to those in animal cells, yet differences at the molecular level, first suggested by analysis of the recently completed (2004) Tetrahymena genome, are turning out to be informative both for mechanistic and evolutionary studies.

Selected Publications

Tsypin, L, and Turkewitz, AP. (in press) The Co-regulation Data Harvester: Automating gene annotation starting from a transcriptome database. SoftwareX.

Kaur H, Sparvoli D, Osakada H, Iwamoto M, Haraguchi T, Turkewitz AP. (2017) 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. 28:1551-1564. (PubMed)

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

Klinger, C.M., Ramirez-Macias, I., Herman, E.K., Turkewitz, A.P., Field, M.C., and J.B. Dacks (2016) Resolving the homology-function relationship through comparative genomicsw of membrane-trafficking machinery and parasite cell biology. Mol. & Biochem. Parasitol. (PubMed)

Kontur, C., Kumar, S., Lan, X., Pritchard, J.K., and A.P. Turkewitz (2016) Whole genome sequencing identifies a novel factor required for secretory granule maturation in Tetrahymena thermophila. G3 (Bethesda). (PubMed)

Kumar, S., Briguglio, J.S., and A.P. Turkewitz (2015) Secretion of polypeptide crystals from Tetrahymena thermophila secretory organelles (mucocysts) depends on processing by a cysteine cathepsin, CTH4. Euk. Cell. 14: 817-33. (PubMed)

Lynch, M., Field, M.C., Goodson, H., Malik, H.S., Pereira-Leal, J.B., Roos, D. S., Turkewitz, A.P., and S. Sazer (2014) Evolutionary Cell Biology: Two Origins, One Objective. Proc. Natl. Acad. Sci. 111: 16990-4. (PubMed)

Briguglio, J.S. and A.P. Turkewitz (2014) Tetrahymena thermophila: a divergent perspective on eukaryotic membrane traffic. J Exp Zool B Mol Dev Evol. 2014 Nov;322(7):500-16. (PubMed)

Kumar, S., Briguglio, J.S., and A.P. Turkewitz (2014) An aspartyl cathepsin, CTH3, is essential for proprotein processing during secretory granule maturation in Tetrahymena thermophila. Mol. Biol. Cell 25: 2444-60. (PubMed)

Briguglio, J.S., Kumar, S., and A.P. Turkewitz (2013) Lysosomal sorting receptors are essential for secretory granule biogenesis in Tetrahymena. J. Cell Biol. 203: 537-550. (PubMed)

Nusblat, A.D., Bright, L.J., and A.P. Turkewitz (2012) Conservation and innovation in Tetrahymena membrane traffic: proteins, lipids, and compartments. Meth. Cell Biol. 109: 141-75. (PubMed)

Amaro, F., Turkewitz, A.P., Martin-Gonzalez, A. and J-C Gutierrez (2011) Whole-cell biosensors for detection of heavy metal ions in environmental samples based on metallothionein promoters from Tetrahymena thermophila. Microbial Biotech. 4: 513-22. (PubMed)

Bright, L., Kambesis, N., Nelson, S.B. and A.P. Turkewitz (2010) Comprehensive analysis reveals dynamic and evolutionary plasticity of Rab GTPases and membrane traffic in Tetrahymena thermophila. PLOS Genetics 6(10): e1001155. (PubMed)

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

Elde, N.C., Long, M. and A.P. Turkewitz. (2007) A role for convergent evolution in the secretory life of cells. Trends Cell Biol. 17: 157-164. (PubMed)

Elde NC, Morgan G, Winey M, Sperling L, Turkewitz AP (2005) Elucidation of Clathrin-Mediated Endocytosis in Tetrahymena Reveals an Evolutionarily Convergent Recruitment of Dynamin. PLoS Genet 1(5) e52. (PubMed)

A. P. Turkewitz (2004) Out with a bang! Tetrahymena as a model system to study secretory granule biogenesis. Traffic. 5(2):63-8. Review. (PubMed)