Reactome | The intraflagellar transport A (IFT-A) complex is required for the transit of GLI:SUFU complexes to the ciliary base

The intraflagellar transport A (IFT-A) complex is required for the transit of GLI:SUFU complexes to the ciliary base

Stable Identifier

R-HSA-5610766

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

ciliary base

ReviewStatus

5/5

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The intraflagellar transport A (IFT-A) complex is required for the transit of GLI:SUFU complexes to the ciliary base

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Vertebrate hedgehog signaling depends on the passage and/or localization of many of the pathway components through the primary cilium (reviewed in Goetz and Anderson, 2010). Although GLI and SUFU proteins are not concentrated in the cilium in the absence of Hh signaling, processing and/or degradation of the transcription factors requires transit through the cilium and basal levels of these proteins can be detected there (Wen et al, 2010; Tukachinsky et al, 2010; Kim et al, 2006; Liu et al, 2005; Haycraft et 2005). Consistent with this, members of both the IFT-B and IFT-A complex, as well as components of the ciliary basal body and the kinesin-2 and dynein motor proteins have been identified as regulators of Hh signaling (Huangfu et al, 2003; Tran et al, 2008; Liu et al, 2005; Houde et al, 2006; Huangfu et al, 2005; May et al, 2005; Cortellino et al, 2009; Vierkotten et al, 2007; Ferrante et al, 2006; Weatherbee et al, 2009; Liem et al, 2012; Qin et al 2011). KIF7, a microtubule-associated kinesin-type motor that negatively regulates the length of axonemal microtubules, is also required for correct localization of GLI:SUFU (He et al, 2014). Finally, a number of PCP pathway effectors have recently been shown to be required for ciliogenesis, and mutations in these genes disrupt GLI processing (Zeng et al, 2010; Gray et al, 2009; Heydeck et al, 2009; Park et al, 2006).

Literature References

PubMed ID	Title	Journal	Year
19767740	The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development Liu, KJ, Weiss, GS, Wlodarczyk, BJ, Blanchard, O, Abitua, PB, Lee, I, Marcotte, EM, Szabo-Rogers, HL, Gray, RS, Finnell, RH, Wallingford, JB	Nat. Cell Biol.	2009
16311594	Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification Zullo, A, Barra, A, Ferrante, MI, Franco, B, Messaddeq, N, Studer, M, Bimonte, S, Dollé, P	Nat. Genet.	2006
16061793	Cilia and Hedgehog responsiveness in the mouse Huangfu, D, Anderson, KV	Proc. Natl. Acad. Sci. U.S.A.	2005
21209331	Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components Ko, HW, Lin, Y, Qin, J, Eggenschwiler, JT, Norman, RX	Proc. Natl. Acad. Sci. U.S.A.	2011
19000668	Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4 Bassi, MR, Champeval, D, Calmont, A, Wang, C, Zaret, KS, Cortellino, S, Jarnik, M, Wang, B, Caretti, E, Larue, L, Burch, J, Bellacosa, A	Dev. Biol.	2009
19776033	A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling Niswander, LA, Weatherbee, SD, Anderson, KV	Hum. Mol. Genet.	2009
15930098	Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors Niswander, LA, Liu, A, Wang, B	Development	2005
16254602	Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function Yoder, BK, Haycraft, CJ, Banizs, B, Aydin-Son, Y, Zhang, Q, Michaud, EJ	PLoS Genet.	2005
19996169	Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus Kim, J, Kato, M, Beachy, PA	Proc. Natl. Acad. Sci. U.S.A.	2009
17553904	Ftm is a novel basal body protein of cilia involved in Shh signalling Dildrop, R, Wang, B, Peters, T, Rüther, U, Vierkotten, J	Development	2007
20154143	Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation Scales, SJ, Hongo, JA, Wen, X, Evangelista, M, Lai, CK, de Sauvage, FJ	Mol. Cell. Biol.	2010
24952464	The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment Liem, KF, He, M, Anderson, KV, Bangs, F, Omelchenko, T, Subramanian, R, Kapoor, TM	Nat. Cell Biol.	2014
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 Ashique, AM, Peterson, AS, Zarbalis, K, Shen, Y, Wang, B, Ericson, J, Reiter, J, May, SR, Karlen, M	Dev. Biol.	2005
20067783	PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals Zeng, H, Liu, A, Hoover, AN	Dev. Biol.	2010
16493421	Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling Haigo, SL, Wallingford, JB, Park, TJ	Nat. Genet.	2006
19666503	Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling Ocbina, PJ, Liem, KF, He, M, Anderson, KV	Proc. Natl. Acad. Sci. U.S.A.	2009
18327258	THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia Turbe-Doan, A, Yoder, BK, Scherz, PJ, Haycraft, CJ, Shah, JV, Chesebro, AL, Beier, DR, Stottmann, RW, Tran, PV, Herron, BJ, Qiu, H, Besschetnova, TY	Nat. Genet.	2008
19877275	Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse Zeng, H, Heydeck, W, Liu, A	Dev. Dyn.	2009
17027958	Hippi is essential for node cilia assembly and Sonic hedgehog signaling Dickinson, RJ, Houtzager, VM, Hayden, MR, Nicholson, DW, Roy, S, Hoodless, PA, Metzler, M, Cullum, R, Montpetit, R, Houde, C, Simpson, EM	Dev. Biol.	2006
14603322	Hedgehog signalling in the mouse requires intraflagellar transport proteins Huangfu, D, Liu, A, Anderson, KV, Murcia, NS, Rakeman, AS, Niswander, L	Nature	2003
20956384	A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes Salic, A, Lopez, LV, Tukachinsky, H	J. Cell Biol.	2010
20395968	The primary cilium: a signalling centre during vertebrate development Anderson, KV, Goetz, SC	Nat. Rev. Genet.	2010