Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication
Abstract Residential stem cells sense extrinsic and intrinsic signals to proliferate accordingly to maintain homeostasis. However, how differentiated cells control stem cell proliferation still remains elusive. Here, we find that Auxilin (Aux) maintains enterocyte (EC) integrity to prevent unlimited...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07954-w |
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| _version_ | 1849225851629993984 |
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| author | Runqi Wang Zhengran Li Jing Wei Ruiyan Kong Xuejing Ren Hang Zhao Danjie Zhang Xiyue Tao Liu Zhouhua Li |
| author_facet | Runqi Wang Zhengran Li Jing Wei Ruiyan Kong Xuejing Ren Hang Zhao Danjie Zhang Xiyue Tao Liu Zhouhua Li |
| author_sort | Runqi Wang |
| collection | DOAJ |
| description | Abstract Residential stem cells sense extrinsic and intrinsic signals to proliferate accordingly to maintain homeostasis. However, how differentiated cells control stem cell proliferation still remains elusive. Here, we find that Auxilin (Aux) maintains enterocyte (EC) integrity to prevent unlimited intestinal stem cell (ISC) proliferation. Depleting aux in ECs leads to excessive ISC proliferation and intestinal homeostasis disruption. Ectopic cytokine production from dying aux-depleted ECs activates JAK/STAT signaling and promotes ISC proliferation. Mechanistically, Aux facilitates anterograde ER-to-Golgi apparatus (GA) vesicle transport by associating with COPII coatomer. Further, the presentation of cell adhesion molecules (CAMs) by ER-to-GA transport is required for intestinal homeostasis. Together, these data demonstrate that Aux maintains EC integrity by mediating ER-to-GA trafficking of CAMs to restrain excessive ISC proliferation. Thus our study uncovers the underlying mechanism of how differentiated cells control stem cell proliferation through inter-cell communication during tissue homeostasis and pathogenesis. |
| format | Article |
| id | doaj-art-899c36c9c3044c30a04d7ccb32fc1f7e |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-899c36c9c3044c30a04d7ccb32fc1f7e2025-08-24T11:54:27ZengNature Publishing GroupCell Death and Disease2041-48892025-08-0116111310.1038/s41419-025-07954-wAuxilin in enterocytes controls intestinal homeostasis through inter-cell communicationRunqi Wang0Zhengran Li1Jing Wei2Ruiyan Kong3Xuejing Ren4Hang Zhao5Danjie Zhang6Xiyue Tao Liu7Zhouhua Li8Laboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityLaboratory of Stem Cell Biology, College of Life Sciences, Capital Normal UniversityAbstract Residential stem cells sense extrinsic and intrinsic signals to proliferate accordingly to maintain homeostasis. However, how differentiated cells control stem cell proliferation still remains elusive. Here, we find that Auxilin (Aux) maintains enterocyte (EC) integrity to prevent unlimited intestinal stem cell (ISC) proliferation. Depleting aux in ECs leads to excessive ISC proliferation and intestinal homeostasis disruption. Ectopic cytokine production from dying aux-depleted ECs activates JAK/STAT signaling and promotes ISC proliferation. Mechanistically, Aux facilitates anterograde ER-to-Golgi apparatus (GA) vesicle transport by associating with COPII coatomer. Further, the presentation of cell adhesion molecules (CAMs) by ER-to-GA transport is required for intestinal homeostasis. Together, these data demonstrate that Aux maintains EC integrity by mediating ER-to-GA trafficking of CAMs to restrain excessive ISC proliferation. Thus our study uncovers the underlying mechanism of how differentiated cells control stem cell proliferation through inter-cell communication during tissue homeostasis and pathogenesis.https://doi.org/10.1038/s41419-025-07954-w |
| spellingShingle | Runqi Wang Zhengran Li Jing Wei Ruiyan Kong Xuejing Ren Hang Zhao Danjie Zhang Xiyue Tao Liu Zhouhua Li Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication Cell Death and Disease |
| title | Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication |
| title_full | Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication |
| title_fullStr | Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication |
| title_full_unstemmed | Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication |
| title_short | Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication |
| title_sort | auxilin in enterocytes controls intestinal homeostasis through inter cell communication |
| url | https://doi.org/10.1038/s41419-025-07954-w |
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