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

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Reaction [BlackBoxEvent]
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
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Nat. Cell Biol. 2009
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
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
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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
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Hum. Mol. Genet. 2009
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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

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PLoS Genet. 2005
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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

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Mol. Cell. Biol. 2010
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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
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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

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Nat. Genet. 2008
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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
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Nature 2003
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Salic, A, Lopez, LV, Tukachinsky, H

J. Cell Biol. 2010
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Anderson, KV, Goetz, SC

Nat. Rev. Genet. 2010
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