Reactome | ARL6:GTP and the BBSome bind ciliary cargo

ARL6:GTP and the BBSome bind ciliary cargo

Stable Identifier

R-HSA-5624126

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

ARL6:GTP and the BBSome bind ciliary cargo

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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-bound 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) Chiang, AP, Nishimura, D, Searby, C, Elbedour, K, Carmi, R, Ferguson, AL, Secrist, J, Braun, T, Casavant, T, Stone, EM, Sheffield, VC	Am. J. Hum. Genet.	2004
20603001	The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia Jin, H, White, SR, Shida, T, Schulz, S, Aguiar, M, Gygi, SP, Bazan, JF, Nachury, MV	Cell	2010
22139371	Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes Zhang, Q, Nishimura, D, Seo, S, Vogel, T, Morgan, DA, Searby, C, Bugge, K, Stone, EM, Rahmouni, K, Sheffield, VC	Proc. Natl. Acad. Sci. U.S.A.	2011
25443296	The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3 Liew, G M, Ye, F, Nager, A R, Murphy, J P, Lee, J S, Aguiar, M, Breslow, DK, Gygi, S, Nachury, MV	DevCell	2014
22072986	A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened Seo, S, Zhang, Q, Bugge, K, Breslow, DK, Searby, CC, Nachury, MV, Sheffield, VC	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? Nachury, MV, Seeley, ES, Jin, H	Annu. Rev. Cell Dev. Biol.	2010
22389062	The emerging role of Arf/Arl small GTPases in cilia and ciliopathies Li, Y, Ling, K, Hu, J	J. Cell. Biochem.	2012
15314642	Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome Fan, Y, Esmail, MA, Ansley, SJ, Blacque, OE, Boroevich, K, Ross, AJ, Moore, SJ, Badano, JL, May-Simera, H, Compton, DS, Green, JS, Lewis, RA, van Haelst, MM, Parfrey, PS, Baillie, DL, Beales, PL, Katsanis, N, Davidson, WS, Leroux, MR	Nat. Genet.	2004