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Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.

Gruner M, Nelson D, Winbush A, Hintz R, Ryu L, Chung SH, Kim K, Gabel CV, van der Linden AM - PLoS Genet. (2014)

Bottom Line: Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression.While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway.Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.

ABSTRACT
Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

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mef-2 mutations and increased calcium signaling suppress the starvation-induced downregulation of srh-234 expression.A, C) Percentage of animals of the indicated genotypes expressing srh-234p::gfp at wild-type levels. Animals (n>150) were examined at 150× magnification for each genotype. B) Relative expression of srh-234p::gfp in ocr-2 and npr-1 mutants compared to wild-type. For strains carrying ADL::egl-19(gf) extrachromosomal arrays (see Material and Methods), data shown is for two independent transgenic lines. Animals (n = 15–20) were examined at 400× magnification for each genotype. * and ** indicates values that are different from that of wild-type animals at P<0.001, and P<0.05, respectively, and # indicates the values that are different between the genotypes compared by brackets at P<0.05 using either a two-sample t-test or a χ2 test of independence. Error bars denote the SEP or SEM.
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pgen-1004707-g006: mef-2 mutations and increased calcium signaling suppress the starvation-induced downregulation of srh-234 expression.A, C) Percentage of animals of the indicated genotypes expressing srh-234p::gfp at wild-type levels. Animals (n>150) were examined at 150× magnification for each genotype. B) Relative expression of srh-234p::gfp in ocr-2 and npr-1 mutants compared to wild-type. For strains carrying ADL::egl-19(gf) extrachromosomal arrays (see Material and Methods), data shown is for two independent transgenic lines. Animals (n = 15–20) were examined at 400× magnification for each genotype. * and ** indicates values that are different from that of wild-type animals at P<0.001, and P<0.05, respectively, and # indicates the values that are different between the genotypes compared by brackets at P<0.05 using either a two-sample t-test or a χ2 test of independence. Error bars denote the SEP or SEM.

Mentions: As calcium signaling plays an important role in the regulation of the KIN-29-dependent str-1 chemoreceptor in AWB neurons [16], we explored the possibility that calcium signaling is also important for regulating srh-234. gf mutations in the voltage-gated calcium channel, egl-19, are predicted to prolong depolarization and result in sustained calcium influx [55]. We found that egl-19(gf) suppressed the starvation-induced downregulation in a wild-type background (Figure 6A), whereas lf mutations in egl-19 and unc-36, but not unc-2, encoding other voltage-gated calcium channels, partially reduce srh-234 expression during feeding (Figure S2). Thus, increased calcium signaling can override the effects of starvation on reducing srh-234 expression. We further show that egl-19(gf) can suppress the reduced srh-234 expression phenotype of npr-1(ad609), daf-2(e1307) and osm-9(ok1667) mutants (Figure 6A) as well as kin-29(oy38) mutants (Table S2). Expression of egl-19(gf) specifically in ADL neurons (ADL::egl-19(gf)) also suppressed the reduced srh-234 expression phenotype of ocr-2(ak47) and npr-1(ad609) mutants in fed conditions (Figure 6B). These results suggest that increased calcium signaling is sufficient in ADL to bypass the requirement of OCR-2, DAF-2 and KIN-29, and NPR-1 pathways in regulating srh-234 expression.


Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.

Gruner M, Nelson D, Winbush A, Hintz R, Ryu L, Chung SH, Kim K, Gabel CV, van der Linden AM - PLoS Genet. (2014)

mef-2 mutations and increased calcium signaling suppress the starvation-induced downregulation of srh-234 expression.A, C) Percentage of animals of the indicated genotypes expressing srh-234p::gfp at wild-type levels. Animals (n>150) were examined at 150× magnification for each genotype. B) Relative expression of srh-234p::gfp in ocr-2 and npr-1 mutants compared to wild-type. For strains carrying ADL::egl-19(gf) extrachromosomal arrays (see Material and Methods), data shown is for two independent transgenic lines. Animals (n = 15–20) were examined at 400× magnification for each genotype. * and ** indicates values that are different from that of wild-type animals at P<0.001, and P<0.05, respectively, and # indicates the values that are different between the genotypes compared by brackets at P<0.05 using either a two-sample t-test or a χ2 test of independence. Error bars denote the SEP or SEM.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4214617&req=5

pgen-1004707-g006: mef-2 mutations and increased calcium signaling suppress the starvation-induced downregulation of srh-234 expression.A, C) Percentage of animals of the indicated genotypes expressing srh-234p::gfp at wild-type levels. Animals (n>150) were examined at 150× magnification for each genotype. B) Relative expression of srh-234p::gfp in ocr-2 and npr-1 mutants compared to wild-type. For strains carrying ADL::egl-19(gf) extrachromosomal arrays (see Material and Methods), data shown is for two independent transgenic lines. Animals (n = 15–20) were examined at 400× magnification for each genotype. * and ** indicates values that are different from that of wild-type animals at P<0.001, and P<0.05, respectively, and # indicates the values that are different between the genotypes compared by brackets at P<0.05 using either a two-sample t-test or a χ2 test of independence. Error bars denote the SEP or SEM.
Mentions: As calcium signaling plays an important role in the regulation of the KIN-29-dependent str-1 chemoreceptor in AWB neurons [16], we explored the possibility that calcium signaling is also important for regulating srh-234. gf mutations in the voltage-gated calcium channel, egl-19, are predicted to prolong depolarization and result in sustained calcium influx [55]. We found that egl-19(gf) suppressed the starvation-induced downregulation in a wild-type background (Figure 6A), whereas lf mutations in egl-19 and unc-36, but not unc-2, encoding other voltage-gated calcium channels, partially reduce srh-234 expression during feeding (Figure S2). Thus, increased calcium signaling can override the effects of starvation on reducing srh-234 expression. We further show that egl-19(gf) can suppress the reduced srh-234 expression phenotype of npr-1(ad609), daf-2(e1307) and osm-9(ok1667) mutants (Figure 6A) as well as kin-29(oy38) mutants (Table S2). Expression of egl-19(gf) specifically in ADL neurons (ADL::egl-19(gf)) also suppressed the reduced srh-234 expression phenotype of ocr-2(ak47) and npr-1(ad609) mutants in fed conditions (Figure 6B). These results suggest that increased calcium signaling is sufficient in ADL to bypass the requirement of OCR-2, DAF-2 and KIN-29, and NPR-1 pathways in regulating srh-234 expression.

Bottom Line: Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression.While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway.Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.

ABSTRACT
Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

Show MeSH