Figure 4. Coordination of food perception and organismal proteostasis.

a-c, g, Western blots showing UbV-GFP and tubulin (TUB). Data derived from at least 3 independent experiments with similar results. Molecular weights are shown in kDa. a, Low concentrations of OP50 alleviate HB101-dependent changes in proteostasis. Worms of indicated genotypes were grown on depicted mixture of HB101 and OP50. b-c, AWC silencing by histamine-gated chloride channel expression (Pceh-36::HisCl). Food-dependent proteostasis defects in WT (b) and mir-71(n4115) (c) are inhibited upon AWC silencing. Age-synchronized L4 larvae were grown on control (-) or histamine (HA) containing plates (10 mM HA) until day 1 of adulthood. d, Schematic overview of the chemotaxis assay: Plates are separated into test and control quadrants. Worms were transferred to the center of the plate. Animals in each quadrant were determined after 1.5 hr. Calculation of the chemotaxis index (CI) is shown below. e, f, AWC-selective expression of tir-1 or mir-71 is important for chemotaxis behavior (E. coli OP50). Chemotaxis assays were performed using worms of the indicated genotypes. Bars show mean values ± SEM obtained from n=9 independent experiments (mean values represented by dots) with at least 66 (e) or 80 animals (f). Statistics were determined by one-way ANOVA with post-hoc test; ns=not significant. g, E. coli treated with Aztreonam (Az) show abnormal cell growth and cannot be ingested by C. elegans. For ingestion control E.coli OP50 expressing GFP (OP50-GFP) were either treated with Az or left untreated before seeding them to NGM plates. Worms were grown on respective bacteria for 6 hr prior to imaging. Fluorescent images of day 1 adult worms. Scale bar: 250 μm. h, i, Food odor affects tir-1 mRNA level. Relative tir-1 mRNA levels measured by qRT-PCR in day 1 adult worms. Age-synchronized worms were grown on OP50 until day 1 of adulthood and transferred to plates without food (-) or Az-treated OP50 (OP50 Az) for 1 h or 4 hr. Data normalized to wild-type (WT) tir-1 level on food (control condition, data not shown). Bars show mean values ± SEM obtained from n=3 biological replicates with 3 technical replicates each (mean values represented by dots); statistics were determined by one-way ANOVA with post-hoc test; ns=not significant). j, Model: Odors related to bacterial food are sensed via ciliated AWC olfactory neurons. The olfactory stimulation of AWCs provokes cell-nonautonomous regulation of ubiquitin-dependent protein degradation and stress resistance in peripheral tissues including the intestine. A key regulator of this food response is the toll receptor domain protein TIR-1, which is dynamically regulated by direct binding between tir-1 mRNA and mir-71 (mir-71/tir-1) in AWC neurons. Absence of olfactory information (food odor) or abrogation of posttranscriptional regulation via mir-71 results in elevated tir-1 level. Chronic upregulation of tir-1 in AWC neurons in mir-71(n4115) alters diet-evoked communication and blocks adjustments of intestinal proteostasis, which correlates with decreased stress tolerance and lifespan.