HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells
HPS1, a BLOC-3 subunit that acts as a guanine nucleotide exchange factor of Rab32/38, may play a role in the removal of VAMP7 during the maturation of large dense core vesicles of Paneth cells. Loss of HPS1 impairs lysozyme secretion and alters the composition of intestinal microbiota, which may exp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.560110/full |
| _version_ | 1819150856500543488 |
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| author | Jiaying Yu Jiaying Yu Xin He Aihua Wei Teng Liu Qin Zhang Ying Pan Zhenhua Hao Lin Yang Yefeng Yuan Zhao Zhang Chang Zhang Chanjuan Hao Zhihua Liu Wei Li |
| author_facet | Jiaying Yu Jiaying Yu Xin He Aihua Wei Teng Liu Qin Zhang Ying Pan Zhenhua Hao Lin Yang Yefeng Yuan Zhao Zhang Chang Zhang Chanjuan Hao Zhihua Liu Wei Li |
| author_sort | Jiaying Yu |
| collection | DOAJ |
| description | HPS1, a BLOC-3 subunit that acts as a guanine nucleotide exchange factor of Rab32/38, may play a role in the removal of VAMP7 during the maturation of large dense core vesicles of Paneth cells. Loss of HPS1 impairs lysozyme secretion and alters the composition of intestinal microbiota, which may explain the susceptibility of HPS-associated inflammatory bowel disease. Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding tendency, and other chronic organ lesions due to defects in tissue-specific lysosome-related organelles (LROs). For some HPS subtypes, such as HPS-1, it is common to have symptoms of HPS-associated inflammatory bowel disease (IBD). However, its underlying mechanism is largely unknown. HPS1 is a subunit of the BLOC-3 complex which functions in the biogenesis of LROs. Large dense core vesicles (LDCVs) in Paneth cells of the intestine are a type of LROs. We here first report the abnormal LDCV morphology (increased number and enlarged size) in HPS1-deficient pale ear (ep) mice. Similar to its role in melanosome maturation, HPS1 plays an important function in the removal of VAMP7 from LDCVs to promote the maturation of LDCVs. The immature LDCVs in ep mice are defective in regulated secretion of lysozyme, a key anti-microbial peptide in the intestine. We observed changes in the composition of intestinal microbiota in both HPS-1 patients and ep mice. These findings provide insights into the underlying mechanism of HPS-associated IBD development, which may be implicated in possible therapeutic intervention of this devastating condition. |
| first_indexed | 2024-12-22T14:24:09Z |
| format | Article |
| id | doaj.art-dea534c247ea4feb840743eab11201c0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T14:24:09Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dea534c247ea4feb840743eab11201c02022-12-21T18:22:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.560110560110HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth CellsJiaying Yu0Jiaying Yu1Xin He2Aihua Wei3Teng Liu4Qin Zhang5Ying Pan6Zhenhua Hao7Lin Yang8Yefeng Yuan9Zhao Zhang10Chang Zhang11Chanjuan Hao12Zhihua Liu13Wei Li14Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaUniversity of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaDepartment of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaInstitute for Immunology, Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, ChinaInstitute for Immunology, Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaUniversity of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaUniversity of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaInstitute for Immunology, Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaHPS1, a BLOC-3 subunit that acts as a guanine nucleotide exchange factor of Rab32/38, may play a role in the removal of VAMP7 during the maturation of large dense core vesicles of Paneth cells. Loss of HPS1 impairs lysozyme secretion and alters the composition of intestinal microbiota, which may explain the susceptibility of HPS-associated inflammatory bowel disease. Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding tendency, and other chronic organ lesions due to defects in tissue-specific lysosome-related organelles (LROs). For some HPS subtypes, such as HPS-1, it is common to have symptoms of HPS-associated inflammatory bowel disease (IBD). However, its underlying mechanism is largely unknown. HPS1 is a subunit of the BLOC-3 complex which functions in the biogenesis of LROs. Large dense core vesicles (LDCVs) in Paneth cells of the intestine are a type of LROs. We here first report the abnormal LDCV morphology (increased number and enlarged size) in HPS1-deficient pale ear (ep) mice. Similar to its role in melanosome maturation, HPS1 plays an important function in the removal of VAMP7 from LDCVs to promote the maturation of LDCVs. The immature LDCVs in ep mice are defective in regulated secretion of lysozyme, a key anti-microbial peptide in the intestine. We observed changes in the composition of intestinal microbiota in both HPS-1 patients and ep mice. These findings provide insights into the underlying mechanism of HPS-associated IBD development, which may be implicated in possible therapeutic intervention of this devastating condition.https://www.frontiersin.org/articles/10.3389/fimmu.2020.560110/fullHermansky-Pudlak syndromeHPS1large dense core vesiclePaneth cellinflammatory bowel diseaseVAMP7 |
| spellingShingle | Jiaying Yu Jiaying Yu Xin He Aihua Wei Teng Liu Qin Zhang Ying Pan Zhenhua Hao Lin Yang Yefeng Yuan Zhao Zhang Chang Zhang Chanjuan Hao Zhihua Liu Wei Li HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells Frontiers in Immunology Hermansky-Pudlak syndrome HPS1 large dense core vesicle Paneth cell inflammatory bowel disease VAMP7 |
| title | HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells |
| title_full | HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells |
| title_fullStr | HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells |
| title_full_unstemmed | HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells |
| title_short | HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells |
| title_sort | hps1 regulates the maturation of large dense core vesicles and lysozyme secretion in paneth cells |
| topic | Hermansky-Pudlak syndrome HPS1 large dense core vesicle Paneth cell inflammatory bowel disease VAMP7 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.560110/full |
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