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Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication
Runqi Wang1, Zhengran Li1, Jing Wei1
1Laboratory of Stem Cell Biology, College of Life Sciences, Capital Normal University, Beijing, China.
Cell Death & Disease
|August 18, 2025
Summary
Auxilin protein maintains intestinal barrier integrity by regulating vesicle transport. This prevents excessive proliferation of intestinal stem cells, crucial for tissue homeostasis.
Area of Science:
- Cell Biology
- Developmental Biology
- Gastroenterology
Background:
- Stem cell proliferation is tightly regulated to maintain tissue homeostasis.
- The mechanisms by which differentiated cells control stem cell proliferation are not fully understood.
Purpose of the Study:
- To investigate the role of Auxilin in controlling intestinal stem cell proliferation.
- To elucidate the molecular mechanisms by which differentiated cells regulate stem cell activity.
Main Methods:
- Depletion of Auxilin in enterocytes (ECs) in a mouse model.
- Analysis of intestinal stem cell (ISC) proliferation and intestinal homeostasis.
- Investigation of JAK/STAT signaling pathway activation.
- Biochemical assays to study ER-to-Golgi transport and COPII coatomer association.
Main Results:
- Auxilin depletion in ECs leads to excessive ISC proliferation and disrupted intestinal homeostasis.
- Dying Auxilin-depleted ECs release cytokines that activate JAK/STAT signaling, promoting ISC proliferation.
- Auxilin facilitates ER-to-Golgi vesicle transport by interacting with COPII.
- ER-to-Golgi transport of cell adhesion molecules (CAMs) is essential for intestinal homeostasis.
Conclusions:
- Auxilin maintains EC integrity and restrains ISC proliferation by mediating ER-to-Golgi trafficking of CAMs.
- This study reveals a mechanism for differentiated cell control over stem cell proliferation via inter-cell communication.
- The findings have implications for understanding tissue homeostasis and pathogenesis.
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