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Research Interests
Ciliary Assembly and the Role of Cilia in Reproductive
Biology
Research Summary
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.
Research Publications
Lucker BF, Behal RH, Qin H, Siron LC, Taggart WS, Rosenbaum JL, Cole DG. 2005 Characterization of the intraflagellar transport complex B core: direct interaction of the IFT81 and IFT74/72 subunits. J Biol Chem. 280(30):27688-96.
Cole DG. 2005 Intraflagellar transport: keeping the motors coordinated. Curr Biol. 15(19):R798-801.
Miller MS, Esparza JM, Lippa AM, Lux FG 3rd, Cole
DG, Dutcher SK. 2005 Mutant Kinesin-2 motor subunits
increase chromosome loss. Mol Biol Cell. 16(8):3810-20.
Cole DG. 2003. The Intraflagellar Transport Machinery of Chlamydomonas reinhardtii. Traffic. 4(7):435-42
Pazour GJ, BL Dickert, Y Vucica, ES Seeley, JL Rosenbaum, GB Witman, and DG Cole. (2000) Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151:709-718.