57 research outputs found
The RHO-1 RhoGTPase modulates fertility and multiple behaviors in adult C. elegans.
No full textThe Rho family of small GTPases are essential during early embryonic development making it difficult to study their functions in adult animals. Using inducible transgenes expressing either a constitutively active version of the single C. elegans Rho ortholog, RHO-1, or an inhibitor of endogenous Rho (C3 transferase), we demonstrate multiple defects caused by altering Rho signaling in adult C. elegans. Changes in RHO-1 signaling in cholinergic neurons affected locomotion, pharyngeal pumping and fecundity. Changes in RHO-1 signaling outside the cholinergic neurons resulted in defective defecation, ovulation, and changes in C. elegans body morphology. Finally both increased and decreased RHO-1 signaling in adults resulted in death within hours. The multiple post-developmental roles for Rho in C. elegans demonstrate that RhoA signaling pathways continue to be used post-developmentally and the resulting phenotypes provide an opportunity to further study post-developmental Rho signaling pathways using genetic screens
Rho deep in thought.
No full textNeuronal communication underlies all aspects of brain function, including learning, memory, and consciousness. How neurons communicate is controlled by both the formation of neuronal connections during neural development and the regulation of neuronal activity in the adult brain. Rho GTPases have a well-known role in neuronal development, and recent studies published in Genes & Development (Steven et al. 2005; McMullan et al. 2006) have demonstrated that they also regulate neuronal activity in the adult brain—at least in Caenorhabditis elegans. Rho in C. elegans acts as part of a network of Gαq pathways that increase neuronal activity by regulating both production and destruction of the second messenger diacylglycerol (DAG), which is a regulator of synaptic vesicle release. In this issue of Genes & Development, Williams et al. (2007) demonstrate that Gαq acts via the UNC-73RhoGEF to increase Rho activity in neurons, and thus increase levels of DAG. The targets of DAG are known and, in one case, a pathway stretching from binding of ligand on the cell surface to changes in synaptic vesicle priming has been mapped out
Chapter 4 A Network of G‐Protein Signaling Pathways Control Neuronal Activity in C. elegans
No full textUNC-13 Interaction with Syntaxin Is Required for Synaptic Transmission
No full textSummaryNeurotransmitter secretion at synapses is controlled by several processes—morphological docking of vesicles at release sites, priming of docked vesicles to make them fusion competent, and calcium-dependent fusion of vesicles with the plasma membrane [1, 2]. In worms, flies, and mice, mutants lacking UNC-13 have defects in vesicle priming [3–5]. Current models propose that UNC-13 primes vesicles by stabilizing Syntaxin's “open” conformation by directly interacting with its amino-terminal regulatory domain [6–8]. However, the functional significance of the UNC-13/Syntaxin interaction has not been tested directly. A truncated protein containing the Munc homology domains (MHD1 and MHD2) and the carboxy-terminal C2 domain partially rescued both the behavioral and secretion defects of unc-13 mutants in C. elegans. A double mutation in MHD2 (F1000A/K1002A) disrupts the UNC-13/Syntaxin interaction. The rate of endogenous synaptic events and the amplitude of nerve-evoked excitatory post-synaptic currents (EPSCs) were both significantly reduced in UNC-13S(F1000A/K1002A). However, the pool of primed (i.e., fusion-competent) vesicles was normal. These results suggest that the UNC-13/Syntaxin interaction is conserved in C. elegans and that, contrary to current models, the UNC-13/Syntaxin interaction is required for nerve-evoked vesicle fusion rather than synaptic-vesicle priming. Thus, UNC-13 may regulate multiple steps of the synaptic-vesicle cycle
Behavioral and immune responses to infection require Gαq- RhoA signaling in C. elegans.
No full textFollowing pathogen infection the hosts' nervous and immune systems react with coordinated responses to the danger. A key question is how the neuronal and immune responses to pathogens are coordinated, are there common signaling pathways used by both responses? Using C. elegans we show that infection by pathogenic strains of M. nematophilum, but not exposure to avirulent strains, triggers behavioral and immune responses both of which require a conserved Gαq-RhoGEF Trio-Rho signaling pathway. Upon infection signaling by the Gαq pathway within cholinergic motorneurons is necessary and sufficient to increase release of the neurotransmitter acetylcholine and increase locomotion rates and these behavioral changes result in C. elegans leaving lawns of M. nematophilum. In the immune response to infection signaling by the Gαq pathway within rectal epithelial cells is necessary and sufficient to cause changes in cell morphology resulting in tail swelling that limits the infection. These Gαq mediated behavioral and immune responses to infection are separate, act in a cell autonomous fashion and activation of this pathway in the appropriate cells can trigger these responses in the absence of infection. Within the rectal epithelium the Gαq signaling pathway cooperates with a Ras signaling pathway to activate a Raf-ERK-MAPK pathway to trigger the cell morphology changes, whereas in motorneurons Gαq signaling triggers behavioral responses independent of Ras signaling. Thus, a conserved Gαq pathway cooperates with cell specific factors in the nervous and immune systems to produce appropriate responses to pathogen. Thus, our data suggests that ligands for Gq coupled receptors are likely to be part of the signals generated in response to M. nematophilum infection
Sensory Regulation of C. elegans Male Mate-Searching Behavior
No full textHow do animals integrate internal drives and external environmental cues to coordinate behaviors? We address this question by studying mate-searching behavior in C. elegans. C. elegans males explore their environment in search of mates (hermaphrodites) and will leave food if mating partners are absent [1]. However, when mates and food coincide, male exploratory behavior is suppressed and males are retained on the food source [1]. We show that the drive to explore is stimulated by male-specific neurons in the tail, the ray neurons. Periodic contact with the hermaphrodite detected through ray neurons changes the male's behavior during periods of no contact and prevents the male from leaving the food source. The hermaphrodite signal is conveyed by male-specific interneurons that are postsynaptic to the rays and that send processes to the major integrative center in the head. This study identifies key parts of the neural circuit that regulates a sexual appetitive behavior in C. elegans
Serotonin Inhibition of Synaptic Transmission Gαo Decreases the Abundance of UNC-13 at Release Sites
No full textAbstractWe show that serotonin inhibits synaptic transmission at C. elegans neuromuscular junctions, and we describe a signaling pathway that mediates this effect. Release of acetylcholine from motor neurons was assayed by measuring the sensitivity of intact animals to the acetylcholinesterase inhibitor aldicarb. By this assay, exogenous serotonin inhibited acetylcholine release, whereas serotonin antagonists stimulated release. The effects of serotonin on synaptic transmission were mediated by GOA-1 (a Gαo subunit) and DGK-1 (a diacylglycerol [DAG] kinase), both of which act in the ventral cord motor neurons. Mutants lacking goa-1 Gαo accumulated abnormally high levels of the DAG-binding protein UNC-13 at motor neuron nerve terminals, suggesting that serotonin inhibits synaptic transmission by decreasing the abundance of UNC-13 at release sites
The Gα12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in <i>C. elegans</i>
No full textIn Caenorhabditis elegans adults, the single Rho GTPase orthologue, RHO-1, stimulates neurotransmitter release at synapses. We show that one of the pathways acting upstream of RHO-1 in acetylcholine (ACh)-releasing motor neurons depends on Gα12 (GPA-12), which acts via the single C. elegans RGS RhoGEF (RHGF-1). Activated GPA-12 has the same effect as activated RHO-1, inducing the accumulation of diacylglycerol and the neuromodulator UNC-13 at release sites, and increased ACh release. We showed previously that RHO-1 stimulates ACh release by two separate pathways-one that requires UNC-13 and a second that does not. We show here that a non-DAG-binding-UNC-13 mutant that partially blocks increased ACh release by activated RHO-1 completely blocks increased ACh release by activated GPA-12. Thus, the upstream GPA-12/RHGF-1 pathway stimulates only a subset of RHO-1 downstream effectors, suggesting that either the RHO-1 effectors require different levels of activated RHO-1 for activation or there are two distinct pools of RHO-1 within C. elegans neurons
Sensory Regulation of C. elegans Male Mate-Searching Behavior
No full textSummaryHow do animals integrate internal drives and external environmental cues to coordinate behaviors? We address this question by studying mate-searching behavior in C. elegans. C. elegans males explore their environment in search of mates (hermaphrodites) and will leave food if mating partners are absent [1]. However, when mates and food coincide, male exploratory behavior is suppressed and males are retained on the food source [1]. We show that the drive to explore is stimulated by male-specific neurons in the tail, the ray neurons. Periodic contact with the hermaphrodite detected through ray neurons changes the male's behavior during periods of no contact and prevents the male from leaving the food source. The hermaphrodite signal is conveyed by male-specific interneurons that are postsynaptic to the rays and that send processes to the major integrative center in the head. This study identifies key parts of the neural circuit that regulates a sexual appetitive behavior in C. elegans
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