Formation of the BBSome

Stable Identifier
R-HSA-5624125
Type
Reaction [binding]
Species
Homo sapiens
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The BBSome is a complex of 8 conserved proteins with roles in ciliary trafficking (Nachury et al, 2007; Loktev et al, 2008; reviewed in Nachury et al, 2010; Hsiao et al, 2012). Mutations in the BBS genes leads to Bardet-Biedl syndrome, a heterogeneous ciliopathy characterized by obesity, blindness, cystic kidney disease, retinitis pigmentosa, polydactyly, mental retardation, and renal failure in some cases (reviewed in Tobin and Beales, 2009). The BBSome is the primary effector of ARL6/BBS3, a small GTPase that recruits the BBSome and associated membrane proteins destined for the cilium to membranes (Jin et al, 2010; Nachury et al, 2007; Zhang et al, 2011; Seo et al 2011). The BBSome also interacts with the RAB8A guanine nucleotide exchange factor RAB3IP, and in this way promotes the recruitment of RAB8A to the cilium (Nachury et al, 2007). Components of the BBSome are enriched in beta propeller and TPR domains and have been shown to form linear arrays on liposomes (Jin et al, 2010). Where these arrays form, and how they contribute to ciliary targeting remains to be elucidated (Jin et al, 2010; reviewed in Nachury et al, 2010).

In mammalian cells, formation of the BBSome depends on a BBS/CCT complex that consists of MKKS/BBS6, BBS10, BBS12 and 6 members of the CCT/TRiC family of chaperonins. The BBS/CCT complex interacts with a subset of the BBSome protein and plays a role in the BBS7 stability, promoting the formation of an intermediate "BBSome core complex" (Seo et al, 2010; Jin et al, 2010; Zhang el al, 2012).

Literature References
PubMed ID Title Journal Year
19421068 The nonmotile ciliopathies

Tobin, JL, Beales, PL

Genet. Med. 2009
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
23351793 Trafficking in and to the primary cilium

Hsiao, YC, Tuz, K, Ferland, RJ

Cilia 2012
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
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
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
22500027 Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome

Zhang, Q, Yu, D, Seo, S, Stone, EM, Sheffield, VC

J. Biol. Chem. 2012
17574030 A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis

Nachury, MV, Loktev, AV, Zhang, Q, Westlake, CJ, Peränen, J, Merdes, A, Slusarski, DC, Scheller, RH, Bazan, JF, Sheffield, VC, Jackson, PK

Cell 2007
20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Seo, S, Baye, LM, Schulz, NP, Beck, JS, Zhang, Q, Slusarski, DC, Sheffield, VC

Proc. Natl. Acad. Sci. U.S.A. 2010
19081074 A BBSome subunit links ciliogenesis, microtubule stability, and acetylation

Loktev, AV, Zhang, Q, Beck, JS, Searby, CC, Scheetz, TE, Bazan, JF, Slusarski, DC, Sheffield, VC, Jackson, PK, Nachury, MV

Dev. Cell 2008
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