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The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles
Microparticles (MPs) are cell–cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570487/ https://www.ncbi.nlm.nih.gov/pubmed/28806752 http://dx.doi.org/10.1371/journal.pbio.2002354 |
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author | Xu, Bing Fu, Ying Liu, Yan Agvanian, Sosse Wirka, Robert C. Baum, Rachel Zhou, Kang Shaw, Robin M. Hong, TingTing |
author_facet | Xu, Bing Fu, Ying Liu, Yan Agvanian, Sosse Wirka, Robert C. Baum, Rachel Zhou, Kang Shaw, Robin M. Hong, TingTing |
author_sort | Xu, Bing |
collection | PubMed |
description | Microparticles (MPs) are cell–cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA), and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR) domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily to the ESCRT pathway for MP biogenesis in mammalian cardiac ventricular cells, identifying elements of a pathway by which cytoplasmic cBIN1 is released into blood. |
format | Online Article Text |
id | pubmed-5570487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55704872017-08-28 The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles Xu, Bing Fu, Ying Liu, Yan Agvanian, Sosse Wirka, Robert C. Baum, Rachel Zhou, Kang Shaw, Robin M. Hong, TingTing PLoS Biol Research Article Microparticles (MPs) are cell–cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA), and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR) domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily to the ESCRT pathway for MP biogenesis in mammalian cardiac ventricular cells, identifying elements of a pathway by which cytoplasmic cBIN1 is released into blood. Public Library of Science 2017-08-14 /pmc/articles/PMC5570487/ /pubmed/28806752 http://dx.doi.org/10.1371/journal.pbio.2002354 Text en © 2017 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Xu, Bing Fu, Ying Liu, Yan Agvanian, Sosse Wirka, Robert C. Baum, Rachel Zhou, Kang Shaw, Robin M. Hong, TingTing The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title | The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title_full | The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title_fullStr | The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title_full_unstemmed | The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title_short | The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles |
title_sort | escrt-iii pathway facilitates cardiomyocyte release of cbin1-containing microparticles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570487/ https://www.ncbi.nlm.nih.gov/pubmed/28806752 http://dx.doi.org/10.1371/journal.pbio.2002354 |
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