C. elegans OSM-9 is a TRPV channel protein involved in sensory transduction and adaptation. Here, we show that distinct sensory functions arise from different combinations of OSM-9 and related OCR TRPV proteins. Both OSM-9 and OCR-2 are essential for several forms of sensory transduction, including olfaction, osmosensation, mechanosensation, and chemosensation. In neurons that express both OSM-9 and OCR-2, tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia. In neurons that express only OSM-9, tagged OSM-9 protein resides in the cell body and acts in sensory adaptation rather than sensory transduction. Thus, alternative combinations of TRPV proteins may direct different functions in distinct subcellular locations. Animals expressing the mammalian TRPV1 (VR1) channel in ASH nociceptor neurons avoid the TRPV1 ligand capsaicin, allowing selective, drug-inducible activation of a specific behavior.

by the fat (fatty acid desaturase) and elo (fatty acid and Jennifer L. Watts 4, * elongation) genes. A gas chromatography (GC)-based 1 Neuroscience Graduate Program genetic screen led to the identification of the fat and elo 2 HHMI and Department of Anatomy mutations, which disrupt the synthesis of long chain 513 Parnassus PUFAs from dietary precursors (Figure 1A) (Watts and

Biologically active peptides are synthesized from inactive preproproteins or peptide precursors by the sequential actions of processing enzymes. Proprotein convertases cleave the precursor at pairs of basic amino acids, which are then removed from the carboxyl terminus of the generated fragments by a specific carboxypeptidase. Caenorhabditis elegans strains lacking proprotein convertase EGL-3 display a severely impaired neuropeptide profile (Husson et al. 2006, J. Neurochem. 98, 1999-2012. In the present study, we examined the role of the C. elegans carboxypeptidase E orthologue EGL-21 in the processing of peptide precursors. More than 100 carboxy-terminally extended neuropeptides were detected in egl-21 mutant strains. These findings suggest that EGL-21 is a major carboxypeptidase involved in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors. The impaired peptide profile of egl-3 and egl-21 mutants is reflected in some similar phenotypes. They both share a severe widening of the intestinal lumen, locomotion defects, and retention of embryos. In addition, egl-3 animals have decreased intestinal fat content. Taken together, these results suggest that EGL-3 and EGL-21 are key enzymes for the proper processing of neuropeptides that control egg-laying, locomotion, fat storage and the nutritional status.

Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme’s non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.