Dataset Information

A RasGRP, C. elegans RGEF-1b, couples external stimuli to behavior by activating LET-60 (Ras) in sensory neurons.

ABSTRACT: RasGRPs, which load GTP onto Ras and Rap1, are expressed in vertebrate and invertebrate neurons. The functions, regulation, and mechanisms of action of neuronal RasGRPs are unknown. Here, we show how C. elegans RGEF-1b, a prototypical neuronal RasGRP, regulates a critical behavior. Chemotaxis to volatile odorants was disrupted in RGEF-1b-deficient (rgef-1?/?) animals and wild-type animals expressing dominant-negative RGEF-1b in AWC sensory neurons. AWC-specific expression of RGEF-1b-GFP restored chemotaxis in rgef-1?/? mutants. Signals disseminated by RGEF-1b in AWC neurons activated a LET-60 (Ras)-MPK-1 (ERK) signaling cascade. Other RGEF-1b and LET-60 effectors were dispensable for chemotaxis. A bifunctional C1 domain controlled intracellular targeting and catalytic activity of RGEF-1b and was essential for sensory signaling in vivo. Chemotaxis was unaffected when Ca²+-binding EF hands and a conserved phosphorylation site of RGEF-1b were inactivated. Diacylglycerol-activated RGEF-1b links external stimuli (odorants) to behavior (chemotaxis) by activating the LET-60-MPK-1 pathway in specific neurons.

SUBMITTER: Chen L

PROVIDER: S-EPMC3081643 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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A RasGRP, C. elegans RGEF-1b, couples external stimuli to behavior by activating LET-60 (Ras) in sensory neurons.

Chen Lu L Fu Ya Y Ren Min M Xiao Bing B Rubin Charles S CS

Neuron 20110401 1

RasGRPs, which load GTP onto Ras and Rap1, are expressed in vertebrate and invertebrate neurons. The functions, regulation, and mechanisms of action of neuronal RasGRPs are unknown. Here, we show how C. elegans RGEF-1b, a prototypical neuronal RasGRP, regulates a critical behavior. Chemotaxis to volatile odorants was disrupted in RGEF-1b-deficient (rgef-1⁻/⁻) animals and wild-type animals expressing dominant-negative RGEF-1b in AWC sensory neurons. AWC-specific expression of RGEF-1b-GFP restored ...[more]

PMID: 21482356

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Project description:To perform the modulation of an assay system for the sensory integration of 2 sensory stimuli that inhibit each other.The assay system for assessing the integrative response to 2 reciprocally-inhibitory sensory stimuli was modulated by changing the metal ion barrier. Moreover, the hen-1, ttx-3 and casy-1 mutants having known defects in integrative response were used to evaluate the modulated assay systems. Based on the examined assay systems, new genes possibly involved in the sensory integration control were identified.In the presence of different metal ion barriers and diacetyl, locomotion behaviors, basic movements, pan-neuronal, cholinergic and GABAergic neuronal GFP expressions, neuronal development, structures of sensory neurons and interneurons, and stress response of nematodes in different regions of examined assay systems were normal, and chemotaxis toward different concentrations of diacetyl and avoidance of different concentrations of metal ions were inhibited. In the first group, most of the nematodes moved to diacetyl by crossing the barrier of Fe(2+), Zn(2+), or Mn(2+). In the second group, almost half of the nematodes moved to diacetyl by crossing the barrier of Ag(+), Cu(2+), Cr(2+), or Cd(2+). In the third group, only a small number of nematodes moved to diacetyl by crossing the barrier of Pb(2+) or Hg(2+). Moreover, when nematodes encountered different metal ion barriers during migration toward diacetyl, the percentage of nematodes moving back and then turning and that of nematodes moving straight to diacetyl were very different. With the aid of examined assay systems, it was found that mutations of fsn-1 that encodes a F-box protein, and its target scd-2 that encodes a receptor tyrosine kinase, caused severe defects in integrative response, and the sensory integration defects of fsn-1 mutants were obviously inhibited by scd-2 mutation.Based on the nematode behaviors in examined assay systems, 3 groups of assay systems were obtained. The first group may be helpful in evaluating or identifying the very subtle deficits in sensory integration, and the third group may be useful for the final confirmation of sensory integration defects of mutants identified in the first or the second group of assay systems. Furthermore, the important association of sensory integration regulation with stabilization or destabilization of synaptic differentiation may exist in C. elegans.

Dataset Information

A RasGRP, C. elegans RGEF-1b, couples external stimuli to behavior by activating LET-60 (Ras) in sensory neurons.

Publications

A RasGRP, C. elegans RGEF-1b, couples external stimuli to behavior by activating LET-60 (Ras) in sensory neurons.

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