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

Stable Identifier
Reaction [omitted]
Homo sapiens
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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
16311594 Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification

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Nat. Genet. 2006
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Gray, RS, Abitua, PB, Wlodarczyk, BJ, Szabo-Rogers, HL, Blanchard, O, Lee, I, Weiss, GS, Liu, KJ, Marcotte, EM, Wallingford, JB, Finnell, RH

Nat. Cell Biol. 2009
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

Qin, J, Lin, Y, Norman, RX, Ko, HW, Eggenschwiler, JT

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

Cortellino, S, Wang, C, Wang, B, Bassi, MR, Caretti, E, Champeval, D, Calmont, A, Jarnik, M, Burch, J, Zaret, KS, Larue, L, Bellacosa, A

Dev. Biol. 2009
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Hum. Mol. Genet. 2009
15930098 Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors

Liu, A, Wang, B, Niswander, LA

Development 2005
16254602 Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function

Haycraft, CJ, Banizs, B, Aydin-Son, Y, Zhang, Q, Michaud, EJ, Yoder, BK

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

Vierkotten, J, Dildrop, R, Peters, T, Wang, B, Rüther, U

Development 2007
20154143 Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation

Wen, X, Lai, CK, Evangelista, M, Hongo, JA, de Sauvage, FJ, Scales, SJ

Mol. Cell. Biol. 2010
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He, M, Subramanian, R, Bangs, F, Omelchenko, T, Liem, KF, Kapoor, TM, Anderson, KV

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

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Dev. Biol. 2005
20067783 PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals

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Dev. Biol. 2010
16493421 Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling

Park, TJ, Haigo, SL, Wallingford, JB

Nat. Genet. 2006
19666503 Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling

Liem, KF, He, M, Ocbina, PJ, 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

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
19877275 Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse

Heydeck, W, Zeng, H, Liu, A

Dev. Dyn. 2009
17027958 Hippi is essential for node cilia assembly and Sonic hedgehog signaling

Houde, C, Dickinson, RJ, Houtzager, VM, Cullum, R, Montpetit, R, Metzler, M, Simpson, EM, Roy, S, Hayden, MR, Hoodless, PA, Nicholson, DW

Dev. Biol. 2006
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Huangfu, D, Liu, A, Rakeman, AS, Murcia, NS, Niswander, L, Anderson, KV

Nature 2003
20956384 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes

Tukachinsky, H, Lopez, LV, Salic, A

J. Cell Biol. 2010
20395968 The primary cilium: a signalling centre during vertebrate development

Goetz, SC, Anderson, KV

Nat. Rev. Genet. 2010
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