Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis
Apoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechani...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/7/1625 |
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| author | Byeongjin Moon Juyeon Lee Sang-Ah Lee Chanhyuk Min Hyunji Moon Deokhwan Kim Susumin Yang Heera Moon Jaeseon Jeon Young-Eun Joo Daeho Park |
| author_facet | Byeongjin Moon Juyeon Lee Sang-Ah Lee Chanhyuk Min Hyunji Moon Deokhwan Kim Susumin Yang Heera Moon Jaeseon Jeon Young-Eun Joo Daeho Park |
| author_sort | Byeongjin Moon |
| collection | DOAJ |
| description | Apoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechanism by which Tim-4 transduces signals to phagocytes during Tim-4-mediated efferocytosis is incompletely understood. Here, we report that Tim-4 collaborates with Mertk during efferocytosis through a biochemical interaction with Mertk. Proximal localization between the two proteins in phagocytes was observed by immunofluorescence and proximal ligation assays. Physical association between Tim-4 and Mertk, which was mediated by an interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk, was also detected with immunoprecipitation. Furthermore, the effect of Mertk on Tim-4-mediated efferocytosis was abolished by GST-Mertk<sup>FnIII</sup>, a soluble form of the fibronectin type-III domain of Mertk that disrupts the interaction between Tim-4 and Mertk. Taken together, the results from our study suggest that a physical interaction between Tim-4 and Mertk is necessary for Mertk to enhance efferocytosis mediated by Tim-4. |
| first_indexed | 2024-03-10T18:39:13Z |
| format | Article |
| id | doaj.art-23e3e9fe514a45d4abb00d3fa5b912ee |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:39:13Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-23e3e9fe514a45d4abb00d3fa5b912ee2023-11-20T05:59:36ZengMDPI AGCells2073-44092020-07-0197162510.3390/cells9071625Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated EfferocytosisByeongjin Moon0Juyeon Lee1Sang-Ah Lee2Chanhyuk Min3Hyunji Moon4Deokhwan Kim5Susumin Yang6Heera Moon7Jaeseon Jeon8Young-Eun Joo9Daeho Park10School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaDepartment of Internal Medicine, Chonnam National Univerity, Gwangju 61469, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaApoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechanism by which Tim-4 transduces signals to phagocytes during Tim-4-mediated efferocytosis is incompletely understood. Here, we report that Tim-4 collaborates with Mertk during efferocytosis through a biochemical interaction with Mertk. Proximal localization between the two proteins in phagocytes was observed by immunofluorescence and proximal ligation assays. Physical association between Tim-4 and Mertk, which was mediated by an interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk, was also detected with immunoprecipitation. Furthermore, the effect of Mertk on Tim-4-mediated efferocytosis was abolished by GST-Mertk<sup>FnIII</sup>, a soluble form of the fibronectin type-III domain of Mertk that disrupts the interaction between Tim-4 and Mertk. Taken together, the results from our study suggest that a physical interaction between Tim-4 and Mertk is necessary for Mertk to enhance efferocytosis mediated by Tim-4.https://www.mdpi.com/2073-4409/9/7/1625efferocytosisTim-4Mertkengulfmentapoptosisphosphatidylserine |
| spellingShingle | Byeongjin Moon Juyeon Lee Sang-Ah Lee Chanhyuk Min Hyunji Moon Deokhwan Kim Susumin Yang Heera Moon Jaeseon Jeon Young-Eun Joo Daeho Park Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis Cells efferocytosis Tim-4 Mertk engulfment apoptosis phosphatidylserine |
| title | Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis |
| title_full | Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis |
| title_fullStr | Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis |
| title_full_unstemmed | Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis |
| title_short | Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis |
| title_sort | mertk interacts with tim 4 to enhance tim 4 mediated efferocytosis |
| topic | efferocytosis Tim-4 Mertk engulfment apoptosis phosphatidylserine |
| url | https://www.mdpi.com/2073-4409/9/7/1625 |
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