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    Novel Acid-Activated Fluorophores Reveal a Dynamic Wave of Protons in the Intestine of Caenorhabditis elegans

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    Bender_ACSChemBiol_2013.pdf (3.965Mb)
    Issue Date
    2013-01-07
    Author
    Bender, Aaron
    Woydziak, Zachary R.
    Fu, Liqiang
    Branden, Michael
    Zhou, Zhenguo
    Ackley, Brian D.
    Peterson, Blake R.
    Publisher
    ACS Chem Biol.
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    © 2012 American Chemical Society
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    Abstract
    Unlike the digestive systems of vertebrate animals, the lumen of the alimentary canal of C. elegans is unsegmented and weakly acidic (pH ~ 4.4), with ultradian fluctuations to pH > 6 every 45 to 50 seconds. To probe the dynamics of this acidity, we synthesized novel acid-activated fluorophores termed Kansas Reds. These dicationic derivatives of rhodamine B become concentrated in the lumen of the intestine of living C. elegans and exhibit tunable pKa values (2.3–5.4), controlled by the extent of fluorination of an alkylamine substituent, that allow imaging of a range of acidic fluids in vivo. Fluorescence video microscopy of animals freely feeding on these fluorophores revealed that acidity in the C. elegans intestine is discontinuous; the posterior intestine contains a large acidic segment flanked by a smaller region of higher pH at the posterior-most end. Remarkably, during the defecation motor program, this hot spot of acidity rapidly moves from the posterior intestine to the anterior-most intestine where it becomes localized for up to 7 seconds every 45 to 50 seconds. Studies of pH-insensitive and base-activated fluorophores as well as mutant and transgenic animals revealed that this dynamic wave of acidity requires the proton exchanger PBO-4, does not involve substantial movement of fluid, and likely involves the sequential activation of proton transporters on the apical surface of intestinal cells. Lacking a specific organ that sequesters low pH, C. elegans compartmentalizes acidity by producing of a dynamic hot spot of protons that rhythmically migrates from the posterior to anterior intestine.
    URI
    http://hdl.handle.net/1808/23524
    DOI
    https://doi.org/10.1021/cb300396j
    Collections
    • Medicinal Chemistry Scholarly Works [225]
    Citation
    Bender, A., Woydziak, Z. R., Fu, L., Branden, M., Zhou, Z., Ackley, B. D., & Peterson, B. R. (2013). Novel Acid-Activated Fluorophores Reveal a Dynamic Wave of Protons in the Intestine of Caenorhabditis elegans. ACS Chemical Biology, 8(3), 636–642. http://doi.org/10.1021/cb300396j

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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