Intraflagellar transport

Stable Identifier
R-HSA-5620924
Type
Pathway
Species
Homo sapiens
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Intraflagellar transport (IFT) is a motor-based process that controls the anterograde and retrograde transport of large protein complexes, ciliary cargo and structural components along the ciliary axoneme (reviewed in Cole and Snell, 2009). IFT particles contain two multiprotein IFT subcomplexes, IFT A and IFT B, with ~6 and ~15 subunits, respectively. Linear arrays of IFT A and IFT B 'trains' assemble at the ciliary base along with the active plus-end directed kinesin-2 motors and the inactive dynein motors and traffic along the microtubules at a rate of ~2 micrometers per second. At the ciliary tip, the IFT trains disassemble, releasing cargo and motors, and smaller IFT trains are subsequently reassembled for retrograde traffic driven by the now active minus-end directed dynein-2 motors. Retrograde trains travel down the length of the axoneme at a rate of ~3 micrometers per second and are disassembled and recycled for further rounds of transport at the ciliary base (reviewed in Taschner et al, 2012; Bhogaraju et al, 2013; Ishikawa et al, 2011). Mutations in kinesin-2 motors or IFT B complex members tend to abrogate cilium formation, while mutations in dynein-2 motor or in IFT A complex members generally result in short, bulging cilia that abnormally accumulate IFT particles. These observations are consistent with a primary role for IFT B and IFT A complexes in anterograde and retrograde transport, respectively (see for instance, Huangfu et al, 2005; Follit et al, 2006; May et al, 2005; Tran et al, 2008; reviwed in Ishikawa et al, 2011). In addition to the IFT A and B complexes, the IFT particles may also contain the multi-protein BBSome complex, which displays typical IFT-like movement along the ciliary axoneme and which is required for cilium biogenesis and delivery and transport of some ciliary cargo (Blaque et al, 2004; Nachury et al, 2007; Ou et al, 2005; Ou et al, 2007; reviewed in Sung and Leroux, 2013; Bhorgaraju et al, 2013).

Literature References
PubMed ID Title Journal Year
21427764 Ciliogenesis: building the cell's antenna

Ishikawa, H, Marshall, WF

Nat. Rev. Mol. Cell Biol. 2011
16775004 The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly

Follit, JA, Tuft, RA, Fogarty, KE, Pazour, GJ

Mol. Biol. Cell 2006
16061793 Cilia and Hedgehog responsiveness in the mouse

Huangfu, D, Anderson, KV

Proc. Natl. Acad. Sci. U.S.A. 2005
16049494 Functional coordination of intraflagellar transport motors

Ou, G, Blacque, OE, Snow, JJ, Leroux, MR, Scholey, JM

Nature 2005
23945166 Intraflagellar transport complex structure and cargo interactions

Bhogaraju, S, Engel, BD, Lorentzen, E

Cilia 2013
17574030 A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis

Nachury, MV, Loktev, AV, Zhang, Q, Westlake, CJ, Peränen, J, Merdes, A, Slusarski, DC, Scheller, RH, Bazan, JF, Sheffield, VC, Jackson, PK

Cell 2007
16229832 Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli

May, SR, Ashique, AM, Karlen, M, Wang, B, Shen, Y, Zarbalis, K, Reiter, J, Ericson, J, Peterson, AS

Dev. Biol. 2005
15231740 Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

Blacque, OE, Reardon, MJ, Li, C, McCarthy, J, Mahjoub, MR, Ansley, SJ, Badano, JL, Mah, AK, Beales, PL, Davidson, WS, Johnsen, RC, Audeh, M, Plasterk, RH, Baillie, DL, Katsanis, N, Quarmby, LM, Wicks, SR, Leroux, MR

Genes Dev. 2004
18327258 THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia

Tran, PV, Haycraft, CJ, Besschetnova, TY, Turbe-Doan, A, Stottmann, RW, Herron, BJ, Chesebro, AL, Qiu, H, Scherz, PJ, Shah, JV, Yoder, BK, Beier, DR

Nat. Genet. 2008
19450523 SnapShot: Intraflagellar transport

Cole, DG, Snell, WJ

Cell 2009
24296415 The roles of evolutionarily conserved functional modules in cilia-related trafficking

Sung, CH, Leroux, MR

Nat. Cell Biol. 2013
17314406 Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles

Ou, G, Koga, M, Blacque, OE, Murayama, T, Ohshima, Y, Schafer, JC, Li, C, Yoder, BK, Leroux, MR, Scholey, JM

Mol. Biol. Cell 2007
22118932 Architecture and function of IFT complex proteins in ciliogenesis

Taschner, M, Bhogaraju, S, Lorentzen, E

Differentiation 2012
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