Loss of <i>C. elegans</i> BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

Blacque, Oliver E.; Reardon, Michael J.; Li, Chunmei; McCarthy, Jonathan; Mahjoub, Moe R.; Ansley, Stephen J.; Badano, José L.; Mah, Allan K.; Beales, Philip L.; Davidson, William S.; Johnsen, Robert; Audeh, Mark J.; Plasterk, Ronald H.A.; Baillie, David L.; Katsanis, Nicholas; Quarmby, Lynne M.; Wicks, Stephen R.; Leroux, Michel R.

doi:10.1101/gad.1194004

Cited by 316 publications

(344 citation statements)

References 43 publications

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“…Here, we used a model organism, C. elegans. In C. elegans, 60 of the 302 neurons of the hermaphrodite are ciliated sensory neurons, and several works have demonstrated that the mutants of IFT-related genes show defects in sensory functions (Cole et al 1998;Signor et al 1999;Qin et al 2001;Haycraft et al 2003;Schafer et al 2003;Blacque et al 2004;Scholey et al 2004;Snow et al 2004;Ou et al 2005;Bell et al 2006;Evans et al 2006). In the present work, we identified nematode IFT-81 and IFT-74, whose C. reinhardtii orthologues were recently shown to form core complex in subcomplex B (Lucker et al 2005), and attempted to elucidate their physiological roles in C. elegans.…”

Section: Introductionmentioning

confidence: 96%

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

Kobayashi¹,

Gengyo-Ando²,

Ishihara³

et al. 2007

Genes to Cells

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Section: Introductionmentioning

confidence: 96%

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

Kobayashi¹,

Gengyo-Ando²,

Ishihara³

et al. 2007

Genes to Cells

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“…Outer dynein arms (ODAs) are also likely cargoes for IFT via interaction with IFT46 through the adaptor protein ODA16 (Hou et al , 2007; Ahmed et al , 2008). Several subunits of the BBSome, a cargo adapter for membrane proteins, have also been demonstrated to move by IFT (Blacque et al , 2004; Lechtreck et al , 2009a) as have several integral and associated membrane proteins (Qin et al , 2005; Huang et al , 2007). …”

Section: Introductionmentioning

confidence: 99%

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

et al. 2016

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Intraflagellar transport (IFT) relies on the IFT complex and is required for ciliogenesis. The IFT‐B complex consists of 9–10 stably associated core subunits and six “peripheral” subunits that were shown to dissociate from the core structure at moderate salt concentration. We purified the six “peripheral” IFT‐B subunits of Chlamydomonas reinhardtii as recombinant proteins and show that they form a stable complex independently of the IFT‐B core. We suggest a nomenclature of IFT‐B1 (core) and IFT‐B2 (peripheral) for the two IFT‐B subcomplexes. We demonstrate that IFT88, together with the N‐terminal domain of IFT52, is necessary to bridge the interaction between IFT‐B1 and B2. The crystal structure of IFT52N reveals highly conserved residues critical for IFT‐B1/IFT‐B2 complex formation. Furthermore, we show that of the three IFT‐B2 subunits containing a calponin homology (CH) domain (IFT38, 54, and 57), only IFT54 binds αβ‐tubulin as a potential IFT cargo, whereas the CH domains of IFT38 and IFT57 mediate the interaction with IFT80 and IFT172, respectively. Crystal structures of IFT54 CH domains reveal that tubulin binding is mediated by basic surface‐exposed residues.

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“…94 Surprisingly, the worm BBS7 homologue moves bidirectionally along the ciliary axoneme and is required for the assembly/function of IFT particles, implicating BBS7 in intraflagellar transport. 100 One of the more interesting ideas to emerge from studies of the BBS proteins in Chlamydomonas, C. elegans, mouse, and humans is that those that associate with centrioles may play roles both in ciliary assembly/function and in cell division. In their centriolar role as basal bodies, they influence cilia function, and in their centriolar role in centrosomes, they influence cell division.…”

Section: Cilia and The Obesity Disorder Bardet-biedl Syndromementioning

confidence: 99%

Cilium-generated signaling and cilia-related disorders

Pan

Wang

Snell

2005

Laboratory Investigation

211

183

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Biologists have long known that humans experience their environment through cilia. Light, odorant, and sound perception depend on these microtubule-filled, complex organelles present on cells in primary sensory tissues. Recently, discoveries on the mechanism of assembly of cilia (flagella) in the lowly, biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance of interest in the organelles along with a recognition of their key sensory roles in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of cellular machinery essential for transporting the protein components of cilia and flagella in all ciliated/ flagellated eukaryotic cells between their site of synthesis in the cell body and their site of assembly at the tip of the flagellum (intraflagellar transport: IFT). Prompted by the surprising observations that disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that PKD proteins are present on the sensory cilia of Caenorhabditis elegans, researchers have made a direct connection between PKD and cilia. At least five (and possibly all) of the seven identified human genes disrupted in PKD and a related disorder nephronophthisis encode proteins expressed in the primary cilia that project into the lumen from the epithelial cells that line renal tubules. Moreover, the renal cilia are flow sensors and at least two of the PKD genes encode ciliary transmembrane proteins essential for mechanosensation. Although their roles have not yet been as clearly identified, cilia also are at the center of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit phenotypes of common human diseases, including obesity and increased incidence of hypertension and diabetes. Five of the eight known BBS genes encode basal body or cilia proteins in mice or humans, and homologues of two of the remaining genes are present in basal bodies/cilia of model organisms. Here we briefly describe the biology of cilia and flagella, we outline how studies on model organisms have led to our current understanding of the roles of these organelles and their proteins in health and disease, and we highlight the notion that the primary cilia present on cells throughout the body, even those on brain neurons, may be essential for as yet undiscovered cilium-generated signaling functions.

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Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

Cited by 316 publications

References 43 publications

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

Cilium-generated signaling and cilia-related disorders

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