Roger D. Sloboda
Ira Allen Eastman Professor of Biological Sciences
Research Area: Cell Biology
Control of Microtubule-Based Intracellular Particle Motility
We use the single celled, bi-flagellate green alga Chlamydomonas to study the factors that regulate the microtubule dependent movements of particles within cells. The microtubules (MTs) of the flagellar axoneme of this organism assemble and continuously turn over at the flagellar tip. The supply to and removal from the tip of the required axonemal components (e. g. tubulin subunits, dynein arms, radial spokes, etc.) are mediated by a motile mechanism called intraflagellar transport (IFT). IFT is essential for the assembly and maintenance of all eukaryotic flagella and cilia, and is characterized by the movement of large protein complexes (IFT particles) from the cell body to the flagellar tip and back to the cell body. The IFT particles consist of ~16 polypeptides partitioned into two complexes, A and B. In a manner analogous to trucks at a construction site, IFT complexes bring material to the flagellar tip, the site of assembly of the MTs. The cargo that IFT transports to the flagellar tip must be unloaded when it arrives there, new cargo must be loaded at the tip to return to the base, and the motor proteins must be turned on and off because it is only at the tip that a change in direction of motility of the IFT particles occurs. Thus, the flagellar tip complex (FTC) contains some very interesting proteins just waiting to be identified and characterized. But why study a small algal cell? As it turns out, genes originally identified in Chlamydomonas that encode proteins involved in IFT turn out to be mutated or missing in a number of human genetic disorders, including seemingly unrelated diseases such as polycystic kidney disease (which afflicts about 1 in 500 individuals), retinitis pigmentosa, situs inversus, polydactyly, and BBS, a syndrome associated with obesity, hypertension, and diabetes (some IFT proteins are also involved in Hedgehog signaling, an important developmental process). What unites these diseases is a need for proper functioning of flagella or cilia during the normal operation of the affected cells or organs, hence the connection to IFT.
Recent Publications
Sloboda, Roger D. and Louisa Howard (2009). Protein Methylation in Full Length Chlamydomonas Flagella. Cell Motility and the Cytoskeleton, 66:650-660.
Schneider, M.J., Ulland, M., and Sloboda, R.D. [2008]. A protein methylation pathway in Chlamydomonas flagella is active during flagellar resorption. Mol. Biol. Cell. 19(10):4319-27.
Sloboda, R.D. and Rosenbaum, J.L. [2007] Making sense of cilia and flagella. J. Cell Biol. 179(4):575-82.
Sloboda, R.D., and Howard, L. [2007]. Localization of EB1, IFT polypeptides, and kinesin-2 in Chlamydomonas flagellar axonemes via immunogold scanning electron microscopy. Cell Motil. Cytoskeleton 64(6):446-60
Sloboda, R.D. [2005]. Intraflagellar transport and the flagellar tip complex. J. Cellular Biochem. 94(2):266-72.
Pedersen, L.B., Geimer, S., Sloboda, R.D., and Rosenbaum, J.L. [2003]. The Microtubule plus end-tracking protein EB1 is localized to the flagellar tip and basal bodies in Chlamydomonas reinhardtii. Curr. Biol. 13(22):1969-74.