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dc.contributor.author
Riazanski, Vladimir
dc.contributor.author
Gabdoulkhakova, Aida G.
dc.contributor.author
Boynton, Lin S.
dc.contributor.author
Eguchi, Raphael R.
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Deriy, Ludmila V.
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Hogarth, D. Kyle
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Loaëc, Nadège
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Oumata, Nassima
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Galons, Hervé
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Brown, Mary E.
dc.contributor.author
Shevchenko, Pavel
dc.contributor.author
Gallan, Alexander J.
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Yoo, Sang Gune
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Naren, Anjaparavanda P.
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Villereal, Mitchel L.
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Beacham, Daniel W.
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Bindokas, Vytautas P.
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Birnbaumer, Lutz
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Meijer, Laurent
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Nelson, Deborah J.
dc.date.available
2018-05-21T19:38:18Z
dc.date.issued
2015-11
dc.identifier.citation
Riazanski, Vladimir; Gabdoulkhakova, Aida G.; Boynton, Lin S.; Eguchi, Raphael R.; Deriy, Ludmila V.; et al.; TRPC6 channel translocation into phagosomal membrane augments phagosomal function; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 47; 11-2015; E6486-E6495
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/45798
dc.description.abstract
Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H(+) into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Phagosome
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Trpc6
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Alveolar Macrophage
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Cystic Fibrosis
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Roscovitine
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
TRPC6 channel translocation into phagosomal membrane augments phagosomal function
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-17T13:50:43Z
dc.journal.volume
112
dc.journal.number
47
dc.journal.pagination
E6486-E6495
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Riazanski, Vladimir. University of Chicago; Estados Unidos
dc.description.fil
Fil: Gabdoulkhakova, Aida G.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Boynton, Lin S.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Eguchi, Raphael R.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Deriy, Ludmila V.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Hogarth, D. Kyle. University of Chicago; Estados Unidos
dc.description.fil
Fil: Loaëc, Nadège. ManRos Therapeutics; Francia
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Fil: Oumata, Nassima. ManRos Therapeutics; Francia
dc.description.fil
Fil: Galons, Hervé. Universite de Paris; Francia
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Fil: Brown, Mary E.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Shevchenko, Pavel. University of Chicago; Estados Unidos
dc.description.fil
Fil: Gallan, Alexander J.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Yoo, Sang Gune. University of Chicago; Estados Unidos
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Fil: Naren, Anjaparavanda P.. Cincinnati Children’s Hospital Medical Center; Estados Unidos
dc.description.fil
Fil: Villereal, Mitchel L.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Beacham, Daniel W.. Thermo Scientific; Estados Unidos
dc.description.fil
Fil: Bindokas, Vytautas P.. University of Chicago; Estados Unidos
dc.description.fil
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
dc.description.fil
Fil: Meijer, Laurent. ManRos Therapeutics; Francia
dc.description.fil
Fil: Nelson, Deborah J.. University of Chicago; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1518966112
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/47/E6486
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664321/
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