Myosin 1b regulates intestinal epithelial morphogenesis via interaction with UNC45A
Céline Revenu1, Corinne Lebreton2, Magda Cannata Serio3
1Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France.
Cell Reports
|December 5, 2024
Summary
Myosin 1b is crucial for intestinal development and is regulated by UNC45A. Its deficiency causes defects in epithelial polarity and gut development, linking it to UNC45A-associated enteropathies.
Area of Science:
- Cell Biology
- Developmental Biology
- Gastroenterology
Background:
- Vesicle trafficking and apicobasal polarity are vital for epithelial morphogenesis.
- UNC45A deficiency is linked to enterocyte polarity defects and severe diarrhea.
- Myosin 1b (MYO1B) is an actin motor involved in membrane dynamics and vesicle transport.
Purpose of the Study:
- To investigate the role of myosin 1b in intestinal epithelium development.
- To explore the relationship between UNC45A and myosin 1b.
- To understand the contribution of myosin 1b to UNC45A-related gut defects.
Main Methods:
- Investigated MYO1B as part of the UNC45A interactome.
- Analyzed myosin 1b stability and aggregation under proteasome inhibition.
- Utilized 3D Caco-2 cell culture and zebrafish larvae models to study lumen formation, spindle orientation, Golgi apparatus, and intestinal morphology.
Main Results:
- MYO1B interacts with UNC45A; its absence leads to myosin 1b degradation.
- Loss of myosin 1b in Caco-2 cells impairs lumen formation, spindle orientation, Golgi integrity, and vesicle trafficking.
- Zebrafish myo1b mutants exhibit intestinal bulb folding defects, terminal web disorganization, and vesicle accumulation, mimicking villous atrophy.
Conclusions:
- Myosin 1b plays a critical, previously unrecognized role in intestinal epithelium development, downstream of UNC45A.
- Myosin 1b's function is essential for maintaining gut integrity and may explain intestinal defects in UNC45A patients.
Keywords:
CP: Cell biologyCP: Developmental biologyIntestinal epitheliumMYO1BMYO5BUNC45AlumenogenesiszebrafishMore Related Videos
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