Dense core secretory granules are vesicles that are responsible for storage and regulated release of a wide variety of polypeptides including hormones, digestive enzymes, and peptide neurotransmitters. Granules store their contents in the cytoplasm of specialized cell types and release these only in graded response to extracellular stimuli. Genetic and environmentally-induced lesions in granule function are connected with serious human diseases, including diabetes and developmental problems. Nonetheless our understanding of the pathway responsible for granule synthesis is still missing important details. The function of secretory granules requires that the specific cargo polypeptides are sorted to vesicles together with membrane proteins that facilitate vesicle docking and fusion. Protein sorting must take place in the trans-Golgi network, but the mechanisms involved are not known. Furthermore, the proteins involved in docking and fusion may be localized to particular regions of the secretory granule membrane.
Our aim i s to understand the molecular bases for the organization of granule membrane proteins both during sorting and in the fully-formed granule. We will do this using the ciliate Tetrahymena thermophila, a genetically-manipulable single-celled system. We have discovered several proteins within Tetrahymena secretory granules that are strong candidates for components interacting with membrane proteins, and we will use a combination of biochemistry and genetics to dissect their function. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Cell Structure and Function (CSF)
Program Officer
Shapiro, Bert I
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Schools of Medicine
United States
Zip Code
Amaro, Francisco; Turkewitz, Aaron P; Martín-González, Ana et al. (2014) 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 27:195-205
Briguglio, Joseph S; Turkewitz, Aaron P (2014) Tetrahymena thermophila: a divergent perspective on membrane traffic. J Exp Zool B Mol Dev Evol 322:500-16
Nusblat, Alejandro D; Bright, Lydia J; Turkewitz, Aaron P (2012) Conservation and innovation in Tetrahymena membrane traffic: proteins, lipids, and compartments. Methods Cell Biol 109:141-75
Poklepovich, Tomas J; Rinaldi, Mauro A; Tomazic, Mariela L et al. (2012) 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 77:1313-20
Amaro, Francisco; Turkewitz, Aaron P; Martin-Gonzalez, Ana et al. (2011) Whole-cell biosensors for detection of heavy metal ions in environmental samples based on metallothionein promoters from Tetrahymena thermophila. Microb Biotechnol 4:513-22
Turkewitz, Aaron P; Bright, Lydia J (2011) A Rab-based view of membrane traffic in the ciliate Tetrahymena thermophila. Small GTPases 2:222-226
Bright, Lydia J; Kambesis, Nichole; Nelson, Scott Brent et al. (2010) Comprehensive analysis reveals dynamic and evolutionary plasticity of Rab GTPases and membrane traffic in Tetrahymena thermophila. PLoS Genet 6:e1001155
Rahaman, Abdur; Miao, Wei; Turkewitz, Aaron P (2009) Independent transport and sorting of functionally distinct protein families in Tetrahymena thermophila dense core secretory granules. Eukaryot Cell 8:1575-83
Rahaman, Abdur; Elde, Nels C; Turkewitz, Aaron P (2008) A dynamin-related protein required for nuclear remodeling in Tetrahymena. Curr Biol 18:1227-33
Elde, Nels C; Long, Manyuan; Turkewitz, Aaron P (2007) A role for convergent evolution in the secretory life of cells. Trends Cell Biol 17:157-64