ARL6:GTP and the BBSome bind ciliary cargo

Stable Identifier
Reaction [binding]
Homo sapiens
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ARL6 is a small GTPase that was also identified as BBS3, a gene that when mutated gives rise to the ciliopathy Bardet-Biedel syndrome (Chiang et al, 2004; Fan et al, 2004). In its GTP-form, membrane-associated ARL6 recruits the BBSome along with BBSome-associated cargo such as SSTR3, MHCR1 or SMO to the cilium (Jin et al, 2010; Zhang et al, 2011; Seo et al, 2011). Binding of IFT27 to the nucleotide-free form of ARL6 may also play a role in promoting the exit of the BBSome from the cilium (Liew et al, 2014). The BBSome, a complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBC9, TTC8/BBS8 and BBIP10 is thought to contribute to ciliary targeting, either by promoting budding of vesicles from the secretory pathway or through lateral diffusion of BBSome-enriched 'rafts' from the plasma membrane as indicated in this reaction (Jin et al, 2010; reviewed in Li et al, 2012; Sung and Leroux, 2013; Nachury et al, 2010). The interaction between the BBSome and ARL6 is mediated by the N-terminal B-propeller domain of BBSome component BBS1 (Jin et al, 2010). BBSome function is negatively regulated by LZTFL1, which forms a complex with the BBSome in the cytosol and inhibits its traffic to the cilium (Seo et al, 2011).
Literature References
PubMed ID Title Journal Year
15258860 Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3)

Casavant, T, Stone, EM, Carmi, R, Elbedour, K, Sheffield, VC, Chiang, AP, Braun, T, Nishimura, D, Secrist, J, Ferguson, AL, Searby, C

Am. J. Hum. Genet. 2004
20603001 The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia

Aguiar, M, Shida, T, Jin, H, Gygi, SP, Nachury, MV, White, SR, Schulz, S, Bazan, JF

Cell 2010
22139371 Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes

Seo, S, Rahmouni, K, Bugge, K, Vogel, T, Morgan, DA, Stone, EM, Zhang, Q, Sheffield, VC, Nishimura, D, Searby, C

Proc. Natl. Acad. Sci. U.S.A. 2011
25443296 The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3

Ye, F, Aguiar, M, Nager, A R, Gygi, S, Murphy, J P, Liew, G M, Lee, J S, Nachury, MV, Breslow, DK

DevCell 2014
22072986 A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened

Seo, S, Searby, CC, Bugge, K, Zhang, Q, Sheffield, VC, Nachury, MV, Breslow, DK

PLoS Genet. 2011
24296415 The roles of evolutionarily conserved functional modules in cilia-related trafficking

Sung, CH, Leroux, MR

Nat. Cell Biol. 2013
19575670 Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier?

Seeley, ES, Jin, H, Nachury, MV

Annu. Rev. Cell Dev. Biol. 2010
22389062 The emerging role of Arf/Arl small GTPases in cilia and ciliopathies

Ling, K, Hu, J, Li, Y

J. Cell. Biochem. 2012
15314642 Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome

Parfrey, PS, Leroux, MR, van Haelst, MM, Moore, SJ, Boroevich, K, Green, JS, Fan, Y, Badano, JL, Ross, AJ, Ansley, SJ, Davidson, WS, Esmail, MA, Beales, PL, Lewis, RA, Katsanis, N, Baillie, DL, May-Simera, H, Blacque, OE, Compton, DS

Nat. Genet. 2004
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