Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

Koelle, Michael R.

doi:10.1895/wormbook.1.75.2

Cited by 48 publications

(60 citation statements)

References 263 publications

(394 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C. elegans allows for a genetic dissection of the roles of neuromodulators on behaviors (Frooninckx et al, 2012; Holden-Dye and Walker, 2013; Koelle, 2016). In addition to biogenic amine neuromodulators, its genome contains 113 genes that may encode up to 250 distinct peptides of three classes (Li and Kim, 2010): the insulin-like (INS) (Pierce et al, 2001), FMRF-amide-related (FLP), and non-insulin/non-FMRF-amide-related (NLP) (Husson et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine modulation sustains the C. elegans forward motor state

Lim

Chitturi

Laskova

et al. 2016

eLife

View full text Add to dashboard Cite

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.DOI: http://dx.doi.org/10.7554/eLife.19887.001

show abstract

Section: Introductionmentioning

confidence: 99%

Neuroendocrine modulation sustains the C. elegans forward motor state

Lim

Chitturi

Laskova

et al. 2016

eLife

View full text Add to dashboard Cite

show abstract

“…In C. elegans, the G q and G o pathways act in opposite ways to regulate locomotion by controlling synaptic vesicle release [82]. G q acts as a positive regulator of acetylcholine release while G o negatively regulates G q signaling, through activation of the G q RGS EAT-16 and the diacylglycerol kinase DGK-1.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, GRK-2 could be a kinase for a GPCR coupled to G o (GOA-1 in C. elegans). The C. elegans G q and G o pathways act in opposite ways to regulate locomotion by controlling acetylcholine release [82]. EGL-30 is a positive regulator of acetylcholine release whereas GOA-1 negatively regulates the EGL-30 pathway through activation of the RGS protein EAT-16 and the diacylglycerol kinase DGK-1.…”

Section: Grk-2 Acts Upstream Of G O To Regulate Locomotionmentioning

confidence: 99%

Dopamine Negatively Modulates the NCA Ion Channels inC. elegans

Topalidou

Cooper

Pereira

et al. 2016

Preprint

View full text Add to dashboard Cite

The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein G q and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the G q -Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit G o signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. Author summaryDopamine is a neurotransmitter that acts in the brain by binding seven transmembrane receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Neuronal G proteins often function by modulating ion channels that control membrane excitability. Here we identify a molecular cascade downstream of dopamine in the nematode C. elegans that involves activation of the dopamine receptor DOP-3, activation of the G protein GOA-1, and inactivation of the NCA-1 and NCA-2 ion channels. We also identify a G protein-coupled receptor kinase (GRK-2) that inactivates the dopamine receptor DOP-3, thus leading to inactivation of GOA-1 and activation of the NCA channels. Thus, this PLOS Genetics | https://doi.org/10.1371/journal.pgen

show abstract

“…In C. elegans neurons, G protein coupled receptors (GPCRs) span the plasma membrane of cilia, and function to detect specific environmental stimuli, including individual pheromone components. When bound to a ligand, the cytoplasmic portion of GPCRs activate their associated G proteins, which function to transduce the sensory signal intracellularly (Koelle 2016). In order to understand the potential molecular mechanism by which endogenous RNAi is required for pheromone sensation, we sought to identify candidate genes involved in sensory signaling that are expressed in ASI, ASJ, and ADL neurons, and exhibit a daf-d phenotype when mutated.…”

Section: Csr-1 Promotes Expression Of G Proteins Required For Dauer Fmentioning

confidence: 99%

Endogenous RNAi Pathways Are Required in Neurons for Dauer Formation in Caenorhabditis elegans

Bharadwaj¹,

Hall

2017

Genetics

View full text Add to dashboard Cite

Animals can adapt to unfavorable environments through changes in physiology or behavior. In the nematode, Caenorhabditis elegans, environmental conditions perceived early in development determine whether the animal enters either the reproductive cycle, or enters into an alternative diapause stage named dauer. Here, we show that endogenous RNAi pathways play a role in dauer formation in crowding (high pheromone), starvation, and high temperature conditions. Disruption of the Mutator proteins or the nuclear Argonaute CSR-1 result in differential dauer-deficient phenotypes that are dependent upon the experienced environmental stress. We provide evidence that the RNAi pathways function in chemosensory neurons for dauer formation, upstream of the TGF-b and insulin signaling pathways. In addition, we show that Mutator MUT-16 expression in a subset of individual pheromone-sensing neurons is sufficient for dauer formation in high pheromone conditions, but not in starvation or high temperature conditions. Furthermore, we also show that MUT-16 and CSR-1 are required for expression of a subset of G proteins with functions in the detection of pheromone components. Together, our data suggest a model where Mutator-amplified siRNAs that associate with the CSR-1 pathway promote expression of genes required for the detection and signaling of environmental conditions to regulate development and behavior in C. elegans. This study highlights a mechanism whereby RNAi pathways mediate the link between environmental stress and adaptive phenotypic plasticity in animals.

show abstract

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

Cited by 48 publications

References 263 publications

Neuroendocrine modulation sustains the C. elegans forward motor state

Neuroendocrine modulation sustains the C. elegans forward motor state

Dopamine Negatively Modulates the NCA Ion Channels inC. elegans

Endogenous RNAi Pathways Are Required in Neurons for Dauer Formation in Caenorhabditis elegans

Contact Info

Product

Resources

About