Intraflagellar Transport: It's not just for cilia anymore

Joel L. Rosenbaum1, Kaiyao Huang1, Chris Wood1, Dennis Diener1, Che-chia Tsao1, Francesca Finetti2, Sylvia Rossi-Paccani2, Gaia Pigino2, Pietro Lupetti2, Gregory Pazour3, George Witman3, Branch Craige3, and Cosima Baldari2

1) Yale University Dept MCDB, New Haven, CT 06520 2) University of Siena, Italy, Dept Evol Biol, 2 Via Alto.13200 3) University of Mass School of Medicine, Worcester, MA 01655

Much of the basic research on IFT (Intraflagellar Transport) in the past decade has been directed at its role in ciliary/flagellar assembly/disassembly. Recently, new aspects of the function of IFT polypeptides have been described. These concern the role of IFT polypeptides not only in the transport and fusion of Golgi-derived vesicles to form the ciliary membrane (Follit and Pazour), but in vesicle fusion and exocytosis in general, including formation of the furrow during cytokinesis (Wood), formation of the IS(Immune Synapse) in lymphocyte T cells (Baldari, Finetti, Rossi), and vesicle fusion at the post synaptic densities of neurons (Wolfrum). Mutations in IFT polypeptides must, therefore, take into account effects on all of these processes. It seems clear that most ciliary membrane polypeptides enter the ciliary compartment by fusion of Golgi-derived vesicles in the peri-centriolar region, followed by lateral transport through the membrane into the cilium. These polypeptides require ciliary recognition sequences (Pazour), probably recognized at the transition region structures, e.g. the nephronocystins 4 and 6-encoded polypeptides (Craige, Witman, Tsao). Less is known about how axonemal proteins enter the ciliary compartment, and we propose that they attach as peripheral proteins to cytoplasmic vesicles destined for fusion in the pericentriolar region followed by transport into the cilium and movement to the tip assembly site in association with the inner aspects of the ciliary membrane, by canonical IFT. Little is known about the removal of ciliary membrane. We provide additional evidence to that already published by others that secretion of functionally active vesicles occurs at the flagellar tip. This may occur in all eukaryotic cilia and may be involved in intercellular signalling. The research described here is supported principally by the NIH (USA), The AIRC and Telethon (Italy) and PKD Foundation.

e-mail address of presenting author: joel.rosenbaum@yale.edu