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A systems-level understanding of cytokine-mediated, intertissue signaling is one of the keys to developing fundamental insight into the links between aging and inflammation. Here, we employed Drosophila, a routine model for analysis of cytokine signaling pathways in higher animals, to identify a receptor for the growth-blocking peptide (GBP) cytokine. Having previously established that the phospholipase C/Ca2+ signaling pathway mediates innate immune responses to GBP, we conducted a dsRNA library screen for genes that modulate Ca2+ mobilization in Drosophila S3 cells. A hitherto orphan G protein coupled receptor, Methuselah-like receptor-10 (Mthl10), was a significant hit. Secondary screening confirmed specific binding of fluorophore-tagged GBP to both S3 cells and recombinant Mthl10-ectodomain. We discovered that the metabolic, immunological, and stress-protecting roles of GBP all interconnect through Mthl10. This we established by Mthl10 knockdown in three fly model systems: in hemocyte-like Drosophila S2 cells, Mthl10 knockdown decreases GBP-mediated innate immune responses; in larvae, Mthl10 knockdown decreases expression of antimicrobial peptides in response to low temperature; in adult flies, Mthl10 knockdown increases mortality rate following infection with Micrococcus luteus and reduces GBP-mediated secretion of insulin-like peptides. We further report that organismal fitness pays a price for the utilization of Mthl10 to integrate all of these various homeostatic attributes of GBP: We found that elevated GBP expression reduces lifespan. Conversely, Mthl10 knockdown extended lifespan. We describe how our data offer opportunities for further molecular interrogation of yin and yang between homeostasis and longevity. [ABSTRACT FROM AUTHOR]

The cricket Modicogryllus siamensis Chopard shows photoperiod-dependent changes in the duration of nymphal development: nymphs become adult within 60 days after hatching, undergoing seven moults under long-day conditions, whereas, under short-day conditions, nymphal development takes much longer (approximately 180 days) with an increased number of moults. Because removal of the compound eyes alters this photoperiodic response, the eyes may be involved in light detection during the photoperiodic response. The role of opsins, expressed in the compound eye, is examined in the present study with reference to the photoperiodic response. Molecular cloning identifies cDNAs of three opsins, opsin-Ultra Violet ( Ms'op- UV), opsin-Blue ( Ms'op-B) and opsin-Long Wave ( Ms'op- LW), and in situ hybridization reveals that the opsin genes are expressed in specific regions of the compound eye in a gene-specific manner. RNA interference (RNAi) technology using the opsin genes results in a partial disruption in the long-day responses; most of the treated crickets showed eight or more moults and up to 23.5% show a prolonged nymphal period that is typical of short-day responses. Under short-day conditions, op- UV RNAi crickets show earlier adult development, whereas no distinct alterations are observed in op-B and op- LW RNAi insects. The results suggest that the opsin genes may play differential roles in the photoperiodic response in the cricket and that the results can be at least partially explained in terms of the external coincidence model of photoperiodic time measurement. [ABSTRACT FROM AUTHOR]

Background: Animals exhibit circadian rhythms with a period of approximately 24 h in various physiological functions, including locomotor activity. This rhythm is controlled by an endogenous oscillatory mechanism, or circadian clock, which consists of cyclically expressed clock genes and their product proteins. cryptochrome ( cry ) genes are thought to be involved in the clock mechanism, and their functions have been examined extensively in holometabolous insects, but in hemimetabolous insects their role is less well understood., Results: In the present study, the role of cry genes was investigated using RNAi technology in a hemimetabolous insect, the cricket Gryllus bimaculatus . Using a molecular cloning approach, we obtained cDNAs for two cry genes: Drosophila -type cry1 ( Gb'cry1 ) and mammalian-type cry2 ( Gb'cry2 ). Gb'cry2 has six splicing variants, most of which showed rhythmic mRNA expression. Gb'cry1 RNAi treatment had only a limited effect at the behavioral and molecular levels, while Gb'cry2 RNAi had a significant effect on behavioral rhythms and molecular oscillatory machinery, alone or in combination with Gb'cry1 RNAi . In Gb'cry1 / Gb'cry2 double-RNAi crickets, most clock genes showed arrhythmic expression, except for timeless , which retained clear rhythmic expression. Molecular analysis revealed that some combination of Gb'cry1 and Gb'cry2 variants suppressed CLK/CYC transcriptional activity in cultured cells., Conclusion: Based on these results, we propose a new model of the cricket's circadian clock, including a molecular oscillatory loop for Gb'cry2 , which can operate independent of the Gb'per / Gb'tim loop.