A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Genetics (Impact Factor: 5.96). 02/2007; 175(1):93-105. DOI: 10.1534/genetics.106.065516
Source: PubMed


Transient receptor potential (TRP) channel subunits form homotetramers that function in sensory transduction. Heteromeric channels also form, but their physiological subunit compositions and functions are largely unknown. We found a dominant-negative mutant of the C. elegans TRPV (vanilloid-type) subunit OCR-2 that apparently incorporates into and inactivates OCR-2 homomers as well as heteromers with the TRPV subunits OCR-1 and -4, resulting in a premature egg-laying defect. This defect is reproduced by knocking out all three OCR genes, but not by any single knockout. Thus a mixture of redundant heteromeric channels prevents premature egg laying. These channels, as well as the G-protein G alpha(o), function in neuroendocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroendocrine cells. The TRPV channel OSM-9, previously suggested to be an obligate heteromeric partner of OCR-2 in sensory neurons, is expressed in the neuroendocrine cells but has no detectable role in egg laying. Our results identify a specific set of heteromeric TRPV channels that redundantly regulate neuroendocrine function and show that a subunit combination that functions in sensory neurons is also present in neuroendocrine cells but has no detectable function in these cells.

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    • "mkate2 encodes a far-red fluorescent protein [38] and was codon-optimized for expression in C. elegans using codon adapter [39]. The tagging was done according to an established strategy into an internal loop of the G protein [40]. The insertion site was analogous to that of a published, functional gfp-tagged goa-1 transgene [41]. "
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    ABSTRACT: Sleep-like states are characterized by massively reduced behavioral activity. Little is known about genetic control of sleep-like behavior. It is also not clear how general activity levels during wake-like behavior influence activity levels during sleep-like behavior. Mutations that increase wake-like activity are generally believed to also increase activity during sleep-like behavior and mutations that decrease wake-like activity are believed to have decreased activity during sleep-like behavior. We studied sleep-like behavior during lethargus in larvae of Caenorhabditis elegans. We looked through a small set of known mutants with altered activity levels. As expected, mutants with increased activity levels typically showed less sleep-like behavior. Among these hyperactive mutants was a gain-of-function mutant of the conserved heterotrimeric G protein subunit Galphaq gene egl-30. We found, however, that an unusual semidominant hypoactive mutant of egl-30 also had reduced sleep-like behavior. While movement was severely reduced and impaired in the semidominant egl-30 mutant, sleep-like behavior was severely reduced: the semidominant egl-30 mutant lacked prolonged periods of complete immobility, reduced spontaneous neural activity less, and reduced responsiveness to stimulation less. egl-30 is a well-known regulator of behavior. Our results suggest that egl-30 controls not only general activity levels, but also differences between wake-like and sleep-like behavior.
    Preview · Article · Sep 2013 · PLoS ONE
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    • "OCR-2 and OSM-9 are homologues of the mammalian TRPV channel genes in C. elegans, and are coexpressed in sensory neurons [34]. Both are expressed in PVD [35-37]. Our results suggest that ocr-2 is required for noxious heat sensation at the midbody, but osm-9 is not (Figure 8b). "
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    • "Both the ocr-2 and osm-9 genes are expressed in PHC and at least osm-9 is expressed in the FLP sensory neurons but not in AFD [15], [32]. We next asked whether expression of ocr-2 and osm-9 in FLP and PHC is sufficient for rescuing the defective Tav response in the mutant. "
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