C. elegans feeding defective mutants have shorter body lengths and increased autophagy

BACKGROUND: Mutations that cause feeding defects in the nematode C. elegans are known to increase life span. Here we show that feeding defective mutants also have a second general trait in common, namely that they are small. RESULTS: Our measurements of the body lengths of a variety of feeding defective mutants, or of a variety of double mutants affecting other pathways that regulate body length in C. elegans, i.e. the DBL-1/TGFβ, TAX-6/calcineurin and the SMA-1/β(H)-spectrin pathways, indicate that food uptake acts as a separate pathway regulating body length. In early stages, before eating begins, feeding defective worms have no defect in body length or, in some cases, have only slightly smaller body length compared to wild-type. A significant difference in body length is first noticeable at later larval stages, a difference that probably correlates with increasing starvation. We also show that autophagy is induced and that the quantity of fat is decreased in starved worms. CONCLUSION: Our results indicate that the long-term starvation seen in feeding-defective C. elegans mutants activates autophagy, and leads to depletion of fat deposits, small cell size and small body size

The Enigmatic Canal-Associated Neurons Regulate Caenorhabditis elegans Larval Development Through a cAMP Signaling Pathway.

Caenorhabditis elegans larval development requires the function of the two Canal-Associated Neurons (CANs): killing the CANs by laser microsurgery or disrupting their development by mutating the gene ceh-10 results in early larval arrest. How these cells promote larval development, however, remains a mystery. In screens for mutations that bypass CAN function, we identified the gene kin-29, which encodes a member of the Salt-Inducible Kinase (SIK) family and a component of a conserved pathway that regulates various C. elegans phenotypes. Like kin-29 loss, gain-of-function mutations in genes that may act upstream of kin-29 or growth in cyclic-AMP analogs bypassed ceh-10 larval arrest, suggesting that a conserved adenylyl cyclase/PKA pathway inhibits KIN-29 to promote larval development, and that loss of CAN function results in dysregulation of KIN-29 and larval arrest. The adenylyl cyclase ACY-2 mediates CAN-dependent larval development: acy-2 mutant larvae arrested development with a similar phenotype to ceh-10 mutants, and the arrest phenotype was suppressed by mutations in kin-29 ACY-2 is expressed predominantly in the CANs, and we provide evidence that the acy-2 functions in the CANs to promote larval development. By contrast, cell-specific expression experiments suggest that kin-29 acts in both the hypodermis and neurons, but not in the CANs. Based on our findings, we propose two models for how ACY-2 activity in the CANs regulates KIN-29 in target cells

C. elegans ten-1 is synthetic lethal with mutations in cytoskeleton regulators, and enhances many axon guidance defective mutants

<p>Abstract</p> <p>Background</p> <p>Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. <it>ten-1 </it>is the <it>C. elegans </it>teneurin homolog with two transcripts, <it>ten-1a </it>and <it>ten-1b</it>, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein. We previously isolated a <it>C. elegans </it>mutant where one pharyngeal neuron was frequently misplaced, and now show that it corresponds to a novel allele of <it>ten-1</it>.</p> <p>Results</p> <p>The novel <it>ten-1(et5) </it>allele is a hypomorph since its post-embryonic phenotype is weaker than the null alleles <it>ten-1(ok641) </it>and <it>ten-1(tm651)</it>. <it>ten-1 </it>mutants have defects in all pharyngeal neurons that we examined, and in vivo reporters show that only the long form of the <it>ten-1 </it>gene is expressed in the pharynx, specifically in six marginal cells and the M2 neurons. Defects in the pharyngeal M2 neurons were enhanced when the <it>ten-1(ok641) </it>mutation was combined with mutations in the following genes: <it>mig-14</it>, <it>unc-5, unc-51, unc-52 </it>and <it>unc-129</it>. None of the body neurons examined show any defects in the <it>ten-1(ok641) </it>mutant, but genetic interaction studies reveal that <it>ten-1(ok641) </it>is synthetic lethal with <it>sax-3, unc-34 </it>and <it>unc-73</it>, and examination of the hypodermal cells in embryos of the <it>ten-1(ok641) </it>mutant point to a role of <it>ten-1 </it>during hypodermal cell morphogenesis.</p> <p>Conclusions</p> <p>Our results are consistent with <it>ten-1 </it>normally providing a function complementary to the cytoskeletal remodeling processes that occur in migrating cells or cells undergoing morphogenesis. It is possible that <it>ten-1 </it>influences the composition/distribution of extracellular matrix.</p

The Adiponectin Receptor Homologs in C. elegans Promote Energy Utilization and Homeostasis

Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs in the nematode C. elegans, named paqr-1, paqr-2 and paqr-3. These are differently expressed in the intestine (the main fat-storing tissue), hypodermis, muscles, neurons and secretory tissues, from which they could exert systemic effects. Analysis of mutants revealed that paqr-1 and -2 are novel metabolic regulators in C. elegans and that they act redundantly but independently from paqr-3. paqr-2 is the most important of the three paqr genes: mutants grow poorly, fail to adapt to growth at low temperature, and have a very high fat content with an abnormal enrichment in long (C20) poly-unsaturated fatty acids when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations in aak-2, the C. elegans homolog of AMPK, or nhr-80, another nuclear hormone receptor gene, suppress the growth phenotype of paqr-2 mutants, probably because they restore the balance between energy expenditure and storage. We conclude that paqr-1 and paqr-2 are receptors that regulate fatty acid metabolism and cold adaptation in C. elegans, that their main function is to promote energy utilization rather than storage, and that PAQR class proteins have regulated metabolism in metazoans for at least 700 million years

Misexpression of acetylcholinesterases in the C. elegans pha-2 mutant accompanies ultrastructural defects in pharyngeal muscle cells

pha-2 is the Caenorhabditis elegans homolog of the vertebrate homeobox gene Hex. Embryonic expression of pha-2 is mostly pharyngeal and the only described mutant allele of pha-2 results in a severe pharyngeal defect in which certain muscle cells (pm5 cells) and neurons are grossly deformed. Here, we performed a detailed characterization of the pha-2 phenotype using cell-type-specific reporters, physical manipulation of the nuclei in pharyngeal muscle cells using optical "tweezers", electron microscopy, staining of the actin cytoskeleton as well as phenotypic rescue and ectopic expression experiments. The main findings of the present study are (i) the pha-2 (ad472) mutation specifically impairs the pharyngeal expression of pha-2; (ii) in the pha-2 mutant, the cytoskeleton of the pm5 cells is measurably weaker than in normal cells and is severely disrupted by large tubular structures and organelles; (iii) the pm5 cells of the pha-2 mutant fail to express the acetylcholinesterase genes ace-1 and ace-2; (iv) ectopic expression of pha-2 can induce ectopic expression of ace-1 and ace-2; and (v) the anc-1 mutant with mislocalized pm5 cell nuclei occasionally shows an isthmus phenotype similar to that of pha-2 worms