Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S]
We previously reported that the endogenous ATP-binding cassette transporter (ABC)A7 strongly associates with phagocytic function rather than biogenesis of high-density lipoprotein (HDL), being regulated by sterol-regulatory element binding protein (SREBP)2. Phagocytic activity was found enhanced by...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520422898 |
| _version_ | 1818735021362511872 |
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| author | Nobukiyo Tanaka Sumiko Abe-Dohmae Noriyuki Iwamoto Michael L. Fitzgerald Shinji Yokoyama |
| author_facet | Nobukiyo Tanaka Sumiko Abe-Dohmae Noriyuki Iwamoto Michael L. Fitzgerald Shinji Yokoyama |
| author_sort | Nobukiyo Tanaka |
| collection | DOAJ |
| description | We previously reported that the endogenous ATP-binding cassette transporter (ABC)A7 strongly associates with phagocytic function rather than biogenesis of high-density lipoprotein (HDL), being regulated by sterol-regulatory element binding protein (SREBP)2. Phagocytic activity was found enhanced by apolipoprotein (apo)A-I and apoA-II more than twice the maximum in J774 and mouse peritoneal macrophages. Therefore we investigated the molecular basis of this reaction in association with the function of ABCA7. Similar to ABCA1, ABCA7 was degraded, likely by calpain, and apoA-I and apoA-II stabilize ABCA7 against degradation. Cell surface biotinylation experiments demonstrated that endogenous ABCA7 predominantly resides on the cell surface and that the apolipoproteins increase the surface ABCA7. The increase of phagocytosis by apolipoproteins was retained in the J774 cells treated with ABCA1 siRNA and in the peritoneal macrophages from ABCA1-knockout mice, but it was abolished in the J774 cells treated with ABCA7 siRNA and in the peritoneal macrophages from ABCA7-knockout mice. Phagocytosis was decreased in the cells in the peritoneal cavity of the ABCA7-knockout mouse compared with the wild-type control. We thus concluded that extracellular helical apolipoproteins augment ABCA7-associated phagocytosis by stabilizing ABCA7. The results demonstrated direct enhancement of the host defense system by HDL components. |
| first_indexed | 2024-12-18T00:14:38Z |
| format | Article |
| id | doaj.art-f92beecc8b8a4d64a3fe5d05a474c1c3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T00:14:38Z |
| publishDate | 2010-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-f92beecc8b8a4d64a3fe5d05a474c1c32022-12-21T21:27:33ZengElsevierJournal of Lipid Research0022-22752010-09-0151925912599Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S]Nobukiyo Tanaka0Sumiko Abe-Dohmae1Noriyuki Iwamoto2Michael L. Fitzgerald3Shinji Yokoyama4Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanTo whom correspondence should be addressed. bc.abedo@med.nagoya-cu.ac.jp; Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanLipid Metabolism Unit, Massachusetts General Hospital, Boston, MA; Partners Healthcare Center for Genetics and Genomics, Harvard Medical School, Boston, MADepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanWe previously reported that the endogenous ATP-binding cassette transporter (ABC)A7 strongly associates with phagocytic function rather than biogenesis of high-density lipoprotein (HDL), being regulated by sterol-regulatory element binding protein (SREBP)2. Phagocytic activity was found enhanced by apolipoprotein (apo)A-I and apoA-II more than twice the maximum in J774 and mouse peritoneal macrophages. Therefore we investigated the molecular basis of this reaction in association with the function of ABCA7. Similar to ABCA1, ABCA7 was degraded, likely by calpain, and apoA-I and apoA-II stabilize ABCA7 against degradation. Cell surface biotinylation experiments demonstrated that endogenous ABCA7 predominantly resides on the cell surface and that the apolipoproteins increase the surface ABCA7. The increase of phagocytosis by apolipoproteins was retained in the J774 cells treated with ABCA1 siRNA and in the peritoneal macrophages from ABCA1-knockout mice, but it was abolished in the J774 cells treated with ABCA7 siRNA and in the peritoneal macrophages from ABCA7-knockout mice. Phagocytosis was decreased in the cells in the peritoneal cavity of the ABCA7-knockout mouse compared with the wild-type control. We thus concluded that extracellular helical apolipoproteins augment ABCA7-associated phagocytosis by stabilizing ABCA7. The results demonstrated direct enhancement of the host defense system by HDL components.http://www.sciencedirect.com/science/article/pii/S0022227520422898ABCA7apoA-IHDLphagocytosisABCA1cholesterol |
| spellingShingle | Nobukiyo Tanaka Sumiko Abe-Dohmae Noriyuki Iwamoto Michael L. Fitzgerald Shinji Yokoyama Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] Journal of Lipid Research ABCA7 apoA-I HDL phagocytosis ABCA1 cholesterol |
| title | Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] |
| title_full | Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] |
| title_fullStr | Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] |
| title_full_unstemmed | Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] |
| title_short | Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7[S] |
| title_sort | helical apolipoproteins of high density lipoprotein enhance phagocytosis by stabilizing atp binding cassette transporter a7 s |
| topic | ABCA7 apoA-I HDL phagocytosis ABCA1 cholesterol |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520422898 |
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