The DAF-7 TGF-β signaling pathway regulates chemosensory receptor gene expression in <i>C. elegans</i>

Nolan, Katherine M.; Sarafi-Reinach, Trina R.; Horne, Jennifer G.; Saffer, Adam M.; Sengupta, Piali

doi:10.1101/gad.1027702

Cited by 65 publications

(91 citation statements)

References 87 publications

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“…Coordinated regulation of all neuron-specific GPCRs would, therefore, coordinately alter responses to all cues sensed by that neuron type. Instead, we and others have previously shown that the expression of different GPCRs in a neuron type is regulated by distinct mechanisms under different external and internal conditions, allowing animals to more precisely modulate their sensory behaviors (Troemel et al 1999;Peckol et al 2001;Lanjuin and Sengupta 2002;Nolan et al 2002;Van Der Linden et al 2007). Diversity and cell specificity in ciliary localization mechanisms may represent yet another layer by which GPCR function and neuronal sensory responses are regulated in C. elegans.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Worms are attracted to, or avoid, different bacteria [68,105,106], and it is not yet known whether these behaviors are mediated primarily via a single bacterially produced chemical, or whether a set of chemicals must be recognized as an ensemble to provide a chemical signature for a specific bacterial strain. Similarly, although a major regulator of worm behavior and development is levels of the constitutively produced dauer pheromone [8][9][10][107][108][109], the neurons that respond to pheromone are also not yet defined. Presumably, males and hermaphrodites also produce signals to attract or repel each other, but these cues and the relevant sensory neurons are unknown [3,4].…”

Section: Mapping Chemicals To Chemosensory Neuronsmentioning

confidence: 99%

“…As each chemosensory neuron expresses multiple chemoreceptors, alteration of expression of individual receptors provides a mechanism by which worms can selectively alter their response to a single chemical sensed by that neuron type, without altering responses to other chemicals. Indeed, individual chemoreceptor genes have been shown to be regulated by a plethora of mechanisms including neuronal activity, internal metabolic state, levels of pheromone, and intercellular signaling [25,63,100,107,108,157] (A. van der Linden, K. Kim and P.S., unpublished observations; Fig. 3a).…”

Section: Modulation Of Chemosensory Behaviorsmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

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“…multiple receptors in each chemosensory neuron (Bargmann 2006b). To selectively modify behavioral response to a single chemical, C. elegans may rely on changing the expression of a particular chemoreceptor gene, rather than altering signaling efficacy of the entire neuron, which would inadvertently affect the response to many chemicals (Peckol et al 2001;Nolan et al 2002). Selectively modulating distinct populations of receptors in this manner may allow C. elegans to fine tune their chemosensory GPCR repertoire and respond appropriately to their environment.…”

Section: Discussionmentioning

confidence: 99%

“…Modulation of GPCR expression by sensory activity is a well-documented phenomenon in C. elegans (Lanjuin and Sengupta 2002;Nolan et al 2002;van der Linden et al 2008). Unlike vertebrates, C. elegans express Figure 5.-The OCR-2(G36E) point mutation functions cell autonomously to restore grk-2 bitter taste responses mediated by ASH.…”

Section: Discussionmentioning

confidence: 99%

Caenorhabditis elegans TRPV Channels Function in a Modality-Specific Pathway to Regulate Response to Aberrant Sensory Signaling

Ezak

Hong²,

Ferkey

2010

Genetics

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Olfaction and some forms of taste (including bitter) are mediated by G protein-coupled signal transduction pathways. Olfactory and gustatory ligands bind to chemosensory G protein-coupled receptors (GPCRs) in specialized sensory cells to activate intracellular signal transduction cascades. G protein-coupled receptor kinases (GRKs) are negative regulators of signaling that specifically phosphorylate activated GPCRs to terminate signaling. Although loss of GRK function usually results in enhanced cellular signaling, Caenorhabditis elegans lacking GRK-2 function are not hypersensitive to chemosensory stimuli. Instead, grk-2 mutant animals do not chemotax toward attractive olfactory stimuli or avoid aversive tastes and smells. We show here that loss-offunction mutations in the transient receptor potential vanilloid (TRPV) channels OSM-9 and OCR-2 selectively restore grk-2 behavioral avoidance of bitter tastants, revealing modality-specific mechanisms for TRPV channel function in the regulation of C. elegans chemosensation. Additionally, a single amino acid point mutation in OCR-2 that disrupts TRPV channel-mediated gene expression, but does not decrease channel function in chemosensory primary signal transduction, also restores grk-2 bitter taste avoidance. Thus, loss of GRK-2 function may lead to changes in gene expression, via OSM-9/OCR-2, to selectively alter the levels of signaling components that transduce or regulate bitter taste responses. Our results suggest a novel mechanism and multiple modality-specific pathways that sensory cells employ in response to aberrant signal transduction.

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The DAF-7 TGF-β signaling pathway regulates chemosensory receptor gene expression in C. elegans

Cited by 65 publications

References 87 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

Generation and modulation of chemosensory behaviors in C. elegans

Caenorhabditis elegans TRPV Channels Function in a Modality-Specific Pathway to Regulate Response to Aberrant Sensory Signaling

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