A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans

Doroquez, David B.; Berciu, Cristina; Anderson, James R.; Sengupta, Piali; Nicastro, Daniela

doi:10.7554/elife.01948

Cited by 184 publications

(382 citation statements)

References 124 publications

(318 reference statements)

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“…As in the corresponding mammalian chemosensory cells, GPCRs required for sensory signaling are concentrated in cilia present at the dendritic endings of a subset of sensory neurons in C. elegans (Troemel et al 1995;Sengupta et al 1996;Kim et al 2009;McGrath et al 2011;Park et al 2012). In the head, 12 pairs of ciliated sensory neuron types are contained in the bilateral amphid organs (Ward et al 1975;Perkins et al 1986;Doroquez et al 2014). Many of the amphid sensory neurons are multimodal; even within a modality such as chemosensation, each neuron responds to many chemicals (Bargmann and Horvitz 1991;Bargmann et al 1993;Hart et al 1995;Maricq et al 1995;Wes and Bargmann 2001;Biron et al 2008;Kuhara et al 2008;Ortiz et al 2009;Bretscher et al 2011).…”

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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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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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“…Astrocytes are glia and can have multiple functions, including provision of nutrients, maintenance of extracellular ion balance, and in some cases release of neurotransmitters. C. elegans also has glia, including sheath cells that envelop the sensory endings of chemosensory and mechanosensory neurons (37,38). For example, the ciliated sensory endings of neurons in the major chemosensory organs of the worm, the amphids and phasmids, traverse the amphid or phasmid sheath cells in narrow membranous tubes and enter the sensillar channel within the sheath cell.…”

Section: Resultsmentioning

confidence: 99%

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Fenk

Bono

2015

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

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Carbon dioxide (CO 2 ) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO 2 , and previous work identified three neuron pairs called "BAG," "AFD," and "ASE" that respond to CO 2 stimuli. Using in vivo Ca 2+ imaging and behavioral analysis, we show that C. elegans can detect CO 2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO 2 with a rise in Ca 2+ . In contrast, glial sheath cells harboring the sensory endings of C. elegans' major chemosensory neurons exhibit strong and sustained decreases in Ca 2+ in response to high CO 2 . Some of these CO 2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO 2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO 2 . Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO 2 is elevated. CO 2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO 2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO 2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.neural circuit | behavioral choice | olfactory system | oviposition | glia M ost living matter creates temporal or spatial gradients of carbon dioxide (CO 2 ). Animals across phylogeny use such gradients to help detect food, conspecifics, or predators (1, 2). The ubiquity of CO 2 suggests that the ecologically relevant information it communicates will depend on the dynamics of the CO 2 stimulus and on context. CO 2 -responsive excitable cells have been identified in mammals (3), arthropods (4), and nematodes (5, 6). However, the number of CO 2 -responsive neurons that are functional in vivo, how they are embedded in neural circuits, and how they shape behavior is unclear.CO 2 crosses membranes readily and dissolves to generate CO 2 (aq), H + , and HCO 3 − . Many proteins whose activity is modified by CO 2 or its solvation products have been identified. pH changes can modulate G protein-coupled receptors (7), Ca 2+ -activated K + channels (8), inwardly rectifying K + channels (9), two pore domain K + channels (10), transient receptor potential (TRP) channels (11, 12), acid-sensing ion channels (ASICs) (13,14), and Pyk2 and ErbB1/2 kinases (15). HCO 3 − modulates soluble adenylate cyclase (16) and transmembrane guanylate cyclases (17); and CO 2 (aq) has been proposed to regulate transmembrane guanylate cyclases (18) and connexin 26 (19) directly. Cells expressing any of these proteins potentially could transduce changes in CO 2 /H + , raising the question: Do animals use a few specific sensory channe...

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“…To investigate whether aging perturbs cilia structure and function in C. elegans, we began by examining the simple rod-like cilia of the ASI sensory neuron pair in the head amphid organs [13,14,37]. ASI cilia were visualized via cell-specific expression of a GFP-tagged SRG-36 pheromone receptor protein, which localizes specifically to ciliary membranes [38] (Fig 1B).…”

Section: Cilia Morphology Is Altered In Late Stages Of Agingmentioning

confidence: 99%

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

Maurya

Cornils

Tereshko

et al. 2017

Mechanisms of Development

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The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies. Author SummaryCilia are 'antenna-like' structures that are present on nearly all cell types in animals. These structures are important for sensing and signaling external cues to the cell. Most cilia are formed by a protein transport process called 'intraflagellar transport' or IFT. Mutations in IFT genes result in severe cilia defects, and are causal to a large number of diverse human disorders called ciliopathies. Since the genes and processes by which cilia are formed are similar across species, studies in experimental models such as the nematode C. elegans can greatly inform our overall understanding of cilia formation and function. Here we report the surprising observation that the structures and functions of severely defective cilia in nematodes with disrupted IFT genes markedly improve upon aging. We find that protein quality control mechanisms that normally decline in aging are required for this age-dependent recovery of cilia structure. Our results raise the possibility that the effects of some mutations in IFT genes can be bypassed under specific conditions, thereby restoring cilia functions.

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A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans

Cited by 184 publications

References 124 publications

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

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

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

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A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans

Cited by 184 publications

References 124 publications

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

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

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

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Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity