Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes

Yang, Shuang; Bahl, Kriti; Chou, Hui‐Ting; Woodsmith, Jonathan; Stelzl, Ulrich; Walz, Thomas; Nachury, Maxence V.

doi:10.7554/elife.55954

Cited by 45 publications

(47 citation statements)

References 78 publications

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“…High-resolution structures are available for several IFT sub-complexes [ 106 – 110 ] and lower resolution structures of complete IFT trains were determined in situ by cryo-ET [ 111 ]. Furthermore, several recent structural cryo-EM studies of mammalian BBSome complexes were recently published [ 112 – 115 ]. The IFT and BBSome complexes were extensively reviewed previously and will not be further covered here [ 105 , 116 ].…”

Section: Intraflagellar Transport On Doublet Microtubulesmentioning

confidence: 99%

Structural insights into the architecture and assembly of eukaryotic flagella

Petriman¹,

Lorentzen²

2020

Microb Cell

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Cilia and flagella are slender projections found on most eukaryotic cells including unicellular organisms such as Chlamydomonas, Trypanosoma and Tetrahymena, where they serve motility and signaling functions. The cilium is a large molecular machine consisting of hundreds of different proteins that are trafficked into the organelle to organize a repetitive microtubule-based axoneme. Several recent studies took advantage of improved cryo-EM methodology to unravel the high-resolution structures of ciliary complexes. These include the recently reported purification and structure determination of axonemal doublet microtubules from the green algae Chlamydomonas reinhardtii, which allows for the modeling of more than 30 associated protein factors to provide deep molecular insight into the architecture and repetitive nature of doublet microtubules. In addition, we will review several recent contributions that dissect the structure and function of ciliary trafficking complexes that ferry structural and signaling components between the cell body and the cilium organelle.

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Section: Intraflagellar Transport On Doublet Microtubulesmentioning

confidence: 99%

Structural insights into the architecture and assembly of eukaryotic flagella

Petriman¹,

Lorentzen²

2020

Microb Cell

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“…In contrast, purified IFT172, an IFT-B component that is also homologous to COPI and ' like WDR35, can not only assemble on liposomes with high affinity but can also bud 50nm vesicles consistent with coatomer sized products (Wang et al, 2018). Together this evolutionary conservation of the BB-Some with coatomer proteins (Jékely and Arendt, 2006;van Dam et al, 2013), interaction with in vitro membranes in presence of ARF like GTPase ARL-6, interaction with phospholipids (Jin et al, 2010;Nachury et al, 2007) and recent cryoEM structures of the complex (Chou et al, 2019;Klink et al, 2020;Singh et al, 2020;Yang et al, 2020) suggest the BBSome may be working as an adaptor for IFT-A mediated cage formation, similar to other coat adaptors for clathrin (i.e.AP1/AP2) or COP (i.e. -, -, -, and -COP for COPI).…”

Section: Discussionmentioning

confidence: 90%

A WDR35-dependent coatomer transports ciliary membrane proteins from the Golgi to the cilia

Quidwai

Hall

Keighren

et al. 2020

Preprint

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Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven transport of cargo within cilia, but how this cargo is selectively transported to cilia and across the diffusion barrier is unclear. WDR35/IFT121 is a component of the IFT-A complex best known for its role in ciliary retrograde transport. In the absence of WDR35, small mutant cilia form but fail to enrich in diverse classes of ciliary membrane proteins. In Wdr35 mouse mutants, the IFT-A peripheral components are degraded and core components accumulate at the transition zone. We reveal deep sequence homology and structural similarity of WDR35 and other IFT-As to the coatomer COPI proteins α and β ′, and demonstrate an accumulation of coat-less vesicles which fail to fuse with Wdr35 mutant cilia. Our data provides the first in-situ evidence of a novel coatomer function for WDR35 likely with other IFT-A proteins in delivering ciliary membrane cargo from the Golgi necessary for cilia elongation.

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“…A recent study has shown that the CTS within the IC3 loop of SSTR3 provides strong binding to a recombinant BBSome core complex, but that the IC3 loop of 5-HT-6 receptor, which is similar to that of rhodopsin, provided only weak interaction (Klink et al, 2017 ). This weak interaction, as well as the presence of an FR motif in rhodopsin helix 8, which also has weak affinity to the BBSome (Klink et al, 2017 ; Yang et al, 2020 ), may support the low presence of rhodopsin in primary cilia (Trivedi and Williams, 2010 ; Trivedi et al, 2012 ; Wang et al, 2012 ; Geneva et al, 2017 ; Chadha et al, 2019 ).…”

Section: The Bbsome In Photoreceptorsmentioning

confidence: 99%

Compartmentalization of Photoreceptor Sensory Cilia

Barnes

Malhotra

Calvert

2021

Front. Cell Dev. Biol.

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Functional compartmentalization of cells is a universal strategy for segregating processes that require specific components, undergo regulation by modulating concentrations of those components, or that would be detrimental to other processes. Primary cilia are hair-like organelles that project from the apical plasma membranes of epithelial cells where they serve as exclusive compartments for sensing physical and chemical signals in the environment. As such, molecules involved in signal transduction are enriched within cilia and regulating their ciliary concentrations allows adaptation to the environmental stimuli. The highly efficient organization of primary cilia has been co-opted by major sensory neurons, olfactory cells and the photoreceptor neurons that underlie vision. The mechanisms underlying compartmentalization of cilia are an area of intense current research. Recent findings have revealed similarities and differences in molecular mechanisms of ciliary protein enrichment and its regulation among primary cilia and sensory cilia. Here we discuss the physiological demands on photoreceptors that have driven their evolution into neurons that rely on a highly specialized cilium for signaling changes in light intensity. We explore what is known and what is not known about how that specialization appears to have driven unique mechanisms for photoreceptor protein and membrane compartmentalization.

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Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes

Cited by 45 publications

References 78 publications

Structural insights into the architecture and assembly of eukaryotic flagella

Structural insights into the architecture and assembly of eukaryotic flagella

A WDR35-dependent coatomer transports ciliary membrane proteins from the Golgi to the cilia

Compartmentalization of Photoreceptor Sensory Cilia

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