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

NC Elde, M Long, AP Turkewitz. The role of convergent evolution in the secretory life of cells. Trends Cell Biol. (in press)

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)

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. (PubMed)

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. (PubMed)

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. (PubMed)

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

Bradshaw, N. R., Chilcoat, N. D., Verbsky, J. W. and Turkewitz, A. P. (2003). "Proprotein processing within secretory dense core granules of Tetrahymena thermophila." J Biol Chem 278: 4087-95. (PubMed)

Chilcoat, N. D., Elde, N. C. and Turkewitz, A. P. (2001). "An antisense approach to phenotype-based gene cloning in Tetrahymena." Proc Natl Acad Sci USA 98: 8709-13. (PubMed)

Turkewitz, A. P., Orias, E. and Kapler, G. (2002). "Functional genomics: the coming of age for Tetrahymena thermophila." Trends Genet 18: 35-40. (PubMed)