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Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx

Phagocytosis of apoptotic cells, called efferocytosis, requires calcium inside and outside of phagocytes. Due to its necessity, calcium flux is sophisticatedly modulated, and the level of intracellular calcium in phagocytes is ultimately elevated during efferocytosis. However, the role of elevated i...

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Autores principales: Yang, Susumin, Min, Chanhyuk, Moon, Hyunji, Moon, Byeongjin, Lee, Juyeon, Jeon, Jaeseon, Kwon, Hagyeong, Jang, Deokyun, Park, Daeho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313764/
https://www.ncbi.nlm.nih.gov/pubmed/37391432
http://dx.doi.org/10.1038/s41419-023-05925-7
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author Yang, Susumin
Min, Chanhyuk
Moon, Hyunji
Moon, Byeongjin
Lee, Juyeon
Jeon, Jaeseon
Kwon, Hagyeong
Jang, Deokyun
Park, Daeho
author_facet Yang, Susumin
Min, Chanhyuk
Moon, Hyunji
Moon, Byeongjin
Lee, Juyeon
Jeon, Jaeseon
Kwon, Hagyeong
Jang, Deokyun
Park, Daeho
author_sort Yang, Susumin
collection PubMed
description Phagocytosis of apoptotic cells, called efferocytosis, requires calcium inside and outside of phagocytes. Due to its necessity, calcium flux is sophisticatedly modulated, and the level of intracellular calcium in phagocytes is ultimately elevated during efferocytosis. However, the role of elevated intracellular calcium in efferocytosis remains elusive. Here, we report that Mertk-mediated intracellular calcium elevation is necessary for internalization of apoptotic cells during efferocytosis. Drastic depletion of intracellular calcium abrogated the internalization step of efferocytosis by delaying phagocytic cup extension and closure. Especially, the defect of phagocytic cup closure for internalization of apoptotic cells was caused by impaired F-actin disassembly and the attenuated interaction of Calmodulin with myosin light chain kinase (MLCK), leading to diminished myosin light chain (MLC) phosphorylation. Genetic and pharmacological impairment of the Calmodulin-MLCK-MLC axis or Mertk-mediated calcium influx also resulted in inefficient efferocytosis due to a defect in internalization of the targets. Taken together, our observations imply that intracellular calcium elevation through Mertk-mediated calcium influx facilitates efferocytosis by inducing myosin II-mediated contraction and F-actin disassembly required for internalization of apoptotic cells.
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spelling pubmed-103137642023-07-02 Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx Yang, Susumin Min, Chanhyuk Moon, Hyunji Moon, Byeongjin Lee, Juyeon Jeon, Jaeseon Kwon, Hagyeong Jang, Deokyun Park, Daeho Cell Death Dis Article Phagocytosis of apoptotic cells, called efferocytosis, requires calcium inside and outside of phagocytes. Due to its necessity, calcium flux is sophisticatedly modulated, and the level of intracellular calcium in phagocytes is ultimately elevated during efferocytosis. However, the role of elevated intracellular calcium in efferocytosis remains elusive. Here, we report that Mertk-mediated intracellular calcium elevation is necessary for internalization of apoptotic cells during efferocytosis. Drastic depletion of intracellular calcium abrogated the internalization step of efferocytosis by delaying phagocytic cup extension and closure. Especially, the defect of phagocytic cup closure for internalization of apoptotic cells was caused by impaired F-actin disassembly and the attenuated interaction of Calmodulin with myosin light chain kinase (MLCK), leading to diminished myosin light chain (MLC) phosphorylation. Genetic and pharmacological impairment of the Calmodulin-MLCK-MLC axis or Mertk-mediated calcium influx also resulted in inefficient efferocytosis due to a defect in internalization of the targets. Taken together, our observations imply that intracellular calcium elevation through Mertk-mediated calcium influx facilitates efferocytosis by inducing myosin II-mediated contraction and F-actin disassembly required for internalization of apoptotic cells. Nature Publishing Group UK 2023-06-30 /pmc/articles/PMC10313764/ /pubmed/37391432 http://dx.doi.org/10.1038/s41419-023-05925-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Susumin
Min, Chanhyuk
Moon, Hyunji
Moon, Byeongjin
Lee, Juyeon
Jeon, Jaeseon
Kwon, Hagyeong
Jang, Deokyun
Park, Daeho
Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title_full Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title_fullStr Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title_full_unstemmed Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title_short Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx
title_sort internalization of apoptotic cells during efferocytosis requires mertk-mediated calcium influx
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313764/
https://www.ncbi.nlm.nih.gov/pubmed/37391432
http://dx.doi.org/10.1038/s41419-023-05925-7
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