Gaertig lab has been exploring the poorly understood mechanisms that govern the assembly and intracellular patterning of microtubule-based organelles, including cilia. We use the free-living ciliate, Tetrahymena thermophila, as a model that offers excellent genetic (forward and reverse), biochemical and imaging approaches. On its surface Tetrahymena carries numerous microtubule-based organelles, including ~1000 cilia, that are arranged in a precise pattern along the anteroposterior and circumferential axes. The properties of individual organelles (such as the length of cilia) are influenced by their position within the cell. We explore the largely unknown mechanisms that control the exact position and properties of microtubular organelles in reference to the overall cellular geometry. We are also interested in the mechanisms that work within an organelle to establish its distinct internal compartments. We have studied how the properties of the core element of cilia, microtubules, are locally modified to create suborganellar compartments.
The ongoing projects in the lab use whole genome sequencing for the discovery of genes whose products affect the position and properties of microtubule-based organelles. Specific projects include: 1) discovery of gene products that affect the placement of microtubular organelles along either the anteroposterior or circumferential cell axes; 2) genetic interactor screens for components of the cilia length regulation pathway; 3) studies on proteins that protect ciliary microtubules against mechanical stress; and 4) identification of proteins that perform structural and signaling roles within the distal tip compartment of cilia.
Wloga, D., Joachimiak, E., Louka, P., and Gaertig, J. (2016). Posttranslational modifications of tubulin and cilia. Cold Spring Harb. Perspect. Biol. Doi: 10.1101/cshperspect.a028159.
Vasudevan, K.K., Yuyang, J., Lechtreck, K., Kushida Y., Alford L., Sale, W., Hennessey, T., and Gaertig J. (2015). Kinesin-13 controls the quantity and quality of tubulin inside cilia. Mol. Biol. Cell. 26: 478-494.
Vasudevan, K.K., Song, K.K., Alford, L.M., Sale, W.S., Dymek, E.E., Smith, E.F., Henessey, T., Urbanska, P., Wloga, D., Dentler, W. Nicastro, D. and Gaertig, J. (2015). FAP206 docks radial spoke 2 and dynein c to ciliary doublet microtubule. Mol. Biol. Cell. 26: 696-710.
Yuyang Y., Lechtreck. K., and Gaertig J. (2015). Total internal reflection microscopy of intraflagellar transport in Tetrahymena thermophila. In: Cilia and Flagella. Methods in Cell Biology. 127: 445-456.
Akella, S., Wloga, D., Kim, J., Starostina N.G., Lyons-Abbott, S., Morrissette, N.S., Dougan S.T., Kipreos, E.T, and Gaertig, J. (2010). MEC-17 is an alpha-tubulin acetyltransferase. Nature. 467: 218-222.
Suryavanshi, S., Eddé, B., Fox, L., Guerrero, S., Griffin, P., Hard, R., Hennessey, T., Kabi, A., Malison, D., Pennock, D., Sale, W., Wloga, D., and Gaertig, J. (2010). Tubulin glutamylation regulates ciliary motility by altering inner dynein arm activity. Current Biology. 20: 435-440.
Wloga, D., Webster, D., Rogowski, K., Bré, M.-H., Levilliers, N., Jerka-Dziadosz, M., Janke, C., Dougan, S.T. and Gaertig, J. (2009). TTLL3 is a tubulin glycine ligase that regulates the assembly of cilia. Dev. Cell. 16: 867-876.
Verhey,K., and Gaertig J. The Tubulin Code. (2007). Cell Cycle, 6: 2152-2160.
Sharma, N., Bryant J., Wloga D., Donaldson R., Davis R.C., Jerka-Dziadosz, M., and Gaertig J. Katanin regulates dynamics of microtubules and biogenesis of motile cilia. (2007). J. Cell Biol. 178: 1065-1079.
Janke, C., Rogowski K., Wloga, D., Regnard,C., Kajava, AV., Strub, J-M., Temurak, N., van Dijk,J., Boucher, D., van Dorsselar, A., Suryavanshi, S., Gaertig, J., and Edde B. (2005). Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Science. 308: 1758-1762
Thazhath R., C. Liu, and J. Gaertig. 2002. Polyglycylation domain of beta-tubulin maintains axonemal architecture and controls progression of cytokinesis in Tetrahymena. Nature Cell Biol. 4: 256-259.