|Department:||Biological Sciences, UI|
|Credentials:||1990 - Ph.D., Washington State University-Biochemistry and Biophysics|
|Office:||Life Sciences South 252|
Ciliary Assembly and the Role of Cilia in Reproductive Biology
The major thrust of our research focuses on a transport process found in both motile and sensory cilia and flagella. This process, intraflagellar transport (IFT), is characterized by the bidirectional movement of membrane-associated protein particles along the length of nearly all eukaryotic cilia and flagella. Work in model organisms ranging from Chlamydomonas green algae to the mouse reveals that this process is required for the assembly of these organelles. Anterograde IFT accomplishes this by carrying axonemal building blocks out to the distal end, which is known to be the site of assembly for the organelle. In contrast, retrograde IFT functions to remove turnover products and membrane proteins from the organelle.
Cilia and flagella are essential in the reproductive biology of many organisms. The male gamete, for example, often employs a motile flagellum in order to move toward the nonmotile female gamete. In some species such as Chlamydomonas, both gametes are flagellated and the initial cell-cell contact is mediated by the organelles. Interestingly, the sites of flagellar contact are characterized by aggregations of the IFT proteins which may mediate flagellar sliding. Consistent with this model, when IFT is disrupted in temperature-sensitive mutants, loss of mating ability is the first observable phenotype. Not surprisingly, disruptions in many of the IFT genes in other model organisms lead to significant reductions in reproductive success. Current research in the lab focuses on the biochemical architecture of the IFT particles and the continued dissection of the cell biological functions of specific IFT machinery.
Behal, R. H. and D. G. Cole (2013). "Analysis of interactions between intraflagellar transport proteins." Methods Enzymol 524: 171-194.
Behal, R. H., et al. (2012). "Subunit interactions and organization of the Chlamydomonas reinhardtii intraflagellar transport complex A proteins." J Biol Chem 287(15): 11689-11703.
Silva, D. A., et al. (2012). "The RABL5 homolog IFT22 regulates the cellular pool size and the amount of IFT particles partitioned to the flagellar compartment in Chlamydomonas reinhardtii." Cytoskeleton (Hoboken) 69(1): 33-48.
Diener, D. R., et al. (2011). "Sequential assembly of flagellar radial spokes." Cytoskeleton (Hoboken) 68(7): 389-400.
Betleja, E. and D. G. Cole (2010). "Ciliary trafficking: CEP290 guards a gated community." Current biology : CB 20(21): R928-931.
Fan, Z. C., R. H. Behal, et al. (2010). "Chlamydomonas IFT70/CrDYF-1 is a core component of IFT particle complex B and is required for flagellar assembly." Molecular biology of the cell 21(15): 2696-2706.
Lucker, B. F., M. S. Miller, et al. (2010). "Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46." J Biol Chem 285(28): 21508-21518.
Behal, R. H., E. Betleja, et al. (2009). "Purification of IFT particle proteins and preparation of recombinant proteins for structural and functional analysis." Methods Cell Biol 93: 179-196.
Cole, D.G. and W.J. Snell, SnapShot: Intraflagellar transport. Cell, 2009. 137(4): p. 784-784
Redding, K. E. and D. G. Cole (2008). "Chlamydomonas: a sexually active, light-harvesting, carbon-reducing, hydrogen-belching 'planimal'. Conference on the Cell & Molecular Biology of Chlamydomonas." EMBO Rep 9(12): 1182-1187.
Ahmed, N. T., et al. (2008). "ODA16 aids axonemal outer row dynein assembly through an interaction with the intraflagellar transport machinery." J Cell Biol 183(2): 313-322.
Wulff, K. D., et al. (2008). "An adaptive system identification approach to optical trap calibration." Opt Express 16(7): 4420-4425.
Flom, G., R.H. Behal, L. Rosen, D.G. Cole, and J.L. Johnson, Definition of the minimal fragments of Sti1 required for dimerization, interaction with Hsp70 and Hsp90 and in vivo functions. Biochem J, 2007. 404(1): p. 159-67.
Cole, D.G., Intraflagellar transport: keeping the motors coordinated. Curr Biol, 2005. 15(19): p. R798-801.
Lucker, B.F., R.H. Behal, H. Qin, L.C. Siron, W.D. Taggart, J.L. Rosenbaum, and D.G. Cole, Characterization of the intraflagellar transport complex B core: direct interaction of the IFT81 and IFT74/72 subunits. J Biol Chem, 2005. 280(30): p. 27688-96.
Miller, M.S., J.M. Esparza, A.M. Lippa, F.G. Lux, 3rd, D.G. Cole, and S.K. Dutcher, Mutant kinesin-2 motor subunits increase chromosome loss. Mol Biol Cell, 2005. 16(8): p. 3810-20.
Pedersen, L. B., et al. (2005). "Chlamydomonas IFT172 is encoded by FLA11, interacts with CrEB1, and regulates IFT at the flagellar tip." Curr Biol 15(3): 262-266.
Mueller, J., et al. (2005). "The FLA3 KAP subunit is required for localization of kinesin-2 to the site of flagellar assembly and processive anterograde intraflagellar transport." Mol Biol Cell 16(3): 1341-1354.
Sun, Z., et al. (2004). "A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney." Development 131(16): 4085-4093.
Qin, H., et al. (2004). "Intraflagellar transport (IFT) cargo: IFT transports flagellar precursors to the tip and turnover products to the cell body." J Cell Biol 164(2): 255-266.
Cole DG. The Intraflagellar Transport Machinery of Chlamydomonas reinhardtii. Traffic, 2003. 4(7):435-42
Cole, D. G. and M. V. Reedy (2003). "Algal morphogenesis: how volvox turns itself inside-out." Curr Biol 13(19): R770-772.
Cole, D. G. (2003). "Intraflagellar transport in the unicellular green alga, Chlamydomonas reinhardtii." Protist 154(2): 181-191.
Pazour, G. J., et al. (2002). "The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance." J Cell Biol 157(1): 103-113.
Deane, J. A., et al. (2001). "Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles." Curr Biol 11(20): 1586-1590.
Center for Reproductive Biology is cited as author affiliation