We explore the poorly understood mechanisms that govern the assembly of microtubule-based organelles, including cilia. We primarly 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 motile cilia, that are used for locomotion, feeding and sensation. The size (length) of individual cilia is dependent on the position within the cell. We use new generation sequencing approaches to identify genes whose products control the length of cilia. We also explore how the cilium becomes subdivided into distinct compartments, with particular interest in the organization of the ciliary distal tip, a region where the cilium grows by elongation of microtubules. We also study how the properties of the core element of cilia, microtubules, are locally adapted (by post-translational modifications of tubulin or by microtubule-binding proteins) to confer certain properties such as resistance to breakage.
Recently we initiated studies of the largely unknown mechanisms that control the position of organelles in reference to the overall cellular geometry.
Specific ongoing projects include: 1) discovery of gene products that affect the placement of organelles along either the anteroposterior or circumferential cell axes; 2) Genetic interactor screens for components of cilium length regulation pathway; 3) studies of 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.
Yuyang J, Maier W., Baumeister R., Minevich G, Joachimiak E., Ruan Z., Kannan, N., Clark, D., Frankel, J. and Gaertig J. (2017). The Hippo pathway maintains the equatorial division plane in the ciliate Tetrahymena. Genetics. Published online 10.1534/genetics.117.200766.
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.