Sensory Ciliogenesis in<i>Caenorhabditis elegans</i>: Assignment of IFT Components into Distinct Modules Based on Transport and Phenotypic Profiles

Ou, Guangshuo; Koga, Makato; Blacque, Oliver E.; Murayama, Takashi; Ohshima, Yasumi; Schafer, James A.; Li, Chunmei; Yoder, Bradley K.; Leroux, Michel R.; Scholey, Jonathan M.

doi:10.1091/mbc.e06-09-0805

Cited by 140 publications

(181 citation statements)

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“…The domain organizations of HICp40 were re-drawn ( Figure 1C). Ou et al identified a novel ciliary protein of F35D11.11B in Caenorhabditis elegans [8]. We re-illustrated the functional domain structures of F35D11.11B ( Figure 1D).…”

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confidence: 70%

DOG 1.0: illustrator of protein domain structures

et al. 2009

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A good picture is worth a thousand words. Schematic diagram of protein domain structures with functional motifs/sites in a concise and illustrative drawing is greatly helpful for a broad readership to grasp the old and novel functions of proteins rapidly. To estimate how many papers contain protein domain graphs, we went through all original research papers (excluding reviews and other articles) in five leading journals in this field, namely

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confidence: 70%

DOG 1.0: illustrator of protein domain structures

et al. 2009

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“…Nature of allele a References bbs-8(nx77) deletion (Blacque et al 2004 deletion (Ou et al 2007 deletion deletion deletion Li et al 2010) arl-13(gk513) deletion missense (Dwyer et al 1998) unc-101(m1) nonsense (Dwyer et al 2001) daf-25(m98) deletion (Jensen et al 2010) daf-25(m362) deletion deletion deletion deletion (Williams et al 2011) nphp-4(tm925) deletion …”

Section: Gene (Allele)mentioning

confidence: 99%

Diverse Cell Type-Specific Mechanisms Localize G Protein-Coupled Receptors to Caenorhabditis elegans Sensory Cilia

Brear

Yoon

Wojtyniak³

et al. 2014

Genetics

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The localization of signaling molecules such as G protein-coupled receptors (GPCRs) to primary cilia is essential for correct signal transduction. Detailed studies over the past decade have begun to elucidate the diverse sequences and trafficking mechanisms that sort and transport GPCRs to the ciliary compartment. However, a systematic analysis of the pathways required for ciliary targeting of multiple GPCRs in different cell types in vivo has not been reported. Here we describe the sequences and proteins required to localize GPCRs to the cilia of the AWB and ASK sensory neuron types in Caenorhabditis elegans. We find that GPCRs expressed in AWB or ASK utilize conserved and novel sequences for ciliary localization, and that the requirement for a ciliary targeting sequence in a given GPCR is different in different neuron types. Consistent with the presence of multiple ciliary targeting sequences, we identify diverse proteins required for ciliary localization of individual GPCRs in AWB and ASK. In particular, we show that the TUB-1 Tubby protein is required for ciliary localization of a subset of GPCRs, implying that defects in GPCR localization may be causal to the metabolic phenotypes of tub-1 mutants. Together, our results describe a remarkable complexity of mechanisms that act in a protein-and cellspecific manner to localize GPCRs to cilia, and suggest that this diversity allows for precise regulation of GPCR-mediated signaling as a function of external and internal context. SIGNALING molecules must be precisely localized to specific subcellular domains to optimize detection and transduction of external stimuli. G protein-coupled receptors (GPCRs) comprise a large family of transmembrane signaling proteins that directly bind and transduce a range of cues including photons, odorants, neurotransmitters, and peptides (Pierce et al. 2002;Kato and Touhara 2009;Demaria and Ngai 2010;Sung and Chuang 2010;Chamero et al. 2012;Frooninckx et al. 2012;Montell 2012;Bathgate et al. 2013). Regulation of GPCR function, including regulation of membrane targeting and trafficking to specific subcellular regions, is a major contributor to the tuning of signaling efficacy and fidelity (e.g., Deretic et al. 1995;Ango et al. 2000;Xia et al. 2003;Esseltine et al. 2012;. However, much remains to be understood regarding the mechanisms by which GPCR trafficking and membrane localization are regulated.GPCR-mediated signal transduction in many cellular contexts requires these proteins to be localized to specialized microtubule-based primary cilia. For example, in photoreceptors and olfactory neurons, efficient sensory signal transduction is mediated via localization of rhodopsin and olfactory receptors, together with other signaling molecules, to photoreceptor outer segments and olfactory neuron cilia, respectively (Insinna and Besharse 2008;Berbari et al. 2009;Pifferi et al. 2010;Deretic and Wang 2012). Receptors in the Hedgehog (Hh) morphogen signaling pathway such as the Smoothened and Patched transmembrane proteins, and the G...

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“…This complex functions in biogenesis of the ciliary membrane (9), trafficking some proteins to or within the ciliary compartment (10), and/or coordinating IFT particle assembly or movement (7,8). Recently, BBSome complexes were shown to form a coat on membranes in vitro (11); this polymerization might underlie some of the functions of the complex.…”

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confidence: 99%

“…BBS proteins are not thought to be essential structural proteins as the basal body and cilium remain largely intact in most mutant BBS models (3)(4)(5). Disruption of individual BBS genes leads to defects in intraflagellar transport (IFT), a process essential for protein trafficking within the cilium (6)(7)(8).…”

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confidence: 99%

Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

Tadenev

Kulaga

May-Simera

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

102

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Bardet-Biedl syndrome (BBS) is a pleiotropic, heterogeneous human disease whose etiology lies primarily in dysfunctional basal bodies and/or cilia. Both BBS patients and several BBS mouse models exhibit impaired olfactory function. To explore the nature of olfactory defects in BBS, a genetic ablation of the mouse Bbs8 gene that incorporates a fluorescent reporter protein was created. The endogenous BBS8 protein and reporter are particularly abundant in olfactory sensory neurons (OSNs), and specific BBS8 antibodies reveal staining in the dendritic knob in a shell-like structure that surrounds the basal bodies. Bbs8-null mice have reduced olfactory responses to a number of odorants, and immunohistochemical analyses reveal a near-complete loss of cilia from OSNs and mislocalization of proteins normally enriched in cilia. To visualize altered protein localization in OSNs, we generated a SLP3 eGFP knock-in mouse and imaged the apical epithelium, including dendritic knobs and proximal cilia, in ex vivo tissue preparations. Additionally, protein reagents that reflect the characteristic neuronal activity of each OSN revealed altered activity in Bbs8-null cells. In addition to previously known defects at the ciliary border, we also observed aberrant targeting of OSN axons to the olfactory bulb; axons expressing the same receptor display reduced fasciculation and project to multiple targets in the olfactory bulb. We suggest that loss of BBS8 leads to a dramatic and variable reduction in cilia, the essential signaling platform for olfaction, which alters the uniformity of responses in populations of OSNs expressing the same receptor, thereby contributing to the observed axon-targeting defects.ciliopathy | olfactory activity | protein trafficking B ardet-Biedl syndrome (BBS), a heterogeneous human disease, encompasses pleiotropic phenotypes including obesity, polydactyly, retinal degeneration, and renal anomalies. The disease, associated with mutations in at least 16 genes, shows complex inheritance. The BBS8 gene was identified via shared homology with BBS4 and was recognized to bear similarity to bacterial pilF; pilF is thought to be involved in the assembly of pili, which are thin, hairlike extensions on prokaryotic cells (1). This prompted the hypothesis that BBS is primarily a disease of the basal body, a microtubule-based modified centriole that nucleates the ciliary axoneme. Subsequent work supports this common etiology of BBS (2). Characterized BBS genes are highly conserved exclusively among ciliated eukaryotes, and most BBS proteins localize to the basal body, centrosome, and/or cilium in ciliated cell-culture models and in ciliated tissues. BBS proteins are not thought to be essential structural proteins as the basal body and cilium remain largely intact in most mutant BBS models (3-5). Disruption of individual BBS genes leads to defects in intraflagellar transport (IFT), a process essential for protein trafficking within the cilium (6-8).Recent studies have found that seven BBS proteins-BBS1, -2, -4, -5, -7, -8,...

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Sensory Ciliogenesis inCaenorhabditis elegans: Assignment of IFT Components into Distinct Modules Based on Transport and Phenotypic Profiles

Cited by 140 publications

References 71 publications

DOG 1.0: illustrator of protein domain structures

DOG 1.0: illustrator of protein domain structures

Diverse Cell Type-Specific Mechanisms Localize G Protein-Coupled Receptors to Caenorhabditis elegans Sensory Cilia

Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting

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