Myosin 1b regulates intestinal epithelial morphogenesis via interaction with UNC45A
Vesicle trafficking and the establishment of apicobasal polarity are essential processes in epithelial morphogenesis. UNC45A deficiency has been reported in a multi-organ syndrome presenting with severe diarrhea associated with enterocyte polarity defects. Myosin 1b, an actin motor able to bind membranes, regulates membrane shaping and vesicle trafficking. Here, we show that MYO1B is part of the UNC45A interactome. In the absence of UNC45A, myosin 1b is degraded and forms aggregates when proteasome activity is inhibited. In 3D Caco-2 cells, lumen formation is impaired in the absence of myosin 1b, associated with spindle orientation defects, Golgi apparatus fragmentation, and trafficking impairment. In zebrafish larvae, loss of myo1b results in intestinal bulb epithelium folding defects associated with terminal web disorganization and vesicle accumulation, reminiscent of villous atrophy. In conclusion, we show that myosin 1b plays an unexpected role in the development of the intestinal epithelium downstream of UNC45A, establishing its contribution in the gut defects reported in UNC45A patients.
Authors
- Priscilla Lépine
- Marion Rosello (ORCID: https://orcid.org/0000-0003-3935-6971)
- Marianna Parlato (ORCID: https://orcid.org/0000-0002-8750-082X)
- Nadine Cerf–Bensussan (ORCID: https://orcid.org/0000-0003-0665-1245)
- Grégoire Michaux (ORCID: https://orcid.org/0000-0003-1222-5461)
- Rémi Duclaux‐Loras (ORCID: https://orcid.org/0000-0002-0182-6184)
- Juliette Vougny (ORCID: https://orcid.org/0000-0002-7361-8405)
- Franck Perez (ORCID: https://orcid.org/0000-0002-9129-9401)
- Céline Revenu (ORCID: https://orcid.org/0000-0003-3697-3739)
- Corinne Lebreton (ORCID: https://orcid.org/0000-0003-1011-8224)
- Julie Stoufflet (ORCID: https://orcid.org/0000-0002-9934-6620)
- Evelyne Coudrier (ORCID: https://orcid.org/0000-0001-6011-8922)
- Karine Duroure (ORCID: https://orcid.org/0000-0002-5959-569X)
- Marie‐Thérèse Prosperi (ORCID: https://orcid.org/0000-0001-7925-7236)
- Filippo Del Bene (ORCID: https://orcid.org/0000-0001-8551-2846)
- Fanny Eggeler (ORCID: https://orcid.org/0009-0001-6803-1984)
- Ophélie Nicolle
- Magda Cannata Serio
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut de la Vision (FR)
- Inserm (FR)
- Université Paris Sciences et Lettres (FR)
- Sorbonne Université (FR)
- Institut de génétique et de développement de Rennes (FR)
- Biologie cellulaire et Cancer (FR)
- Institut des Maladies Génétiques Imagine (FR)
- Génétique et biologie du développement (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114941
- Citations
- 2
- Primary Topic
- Genetic and Kidney Cyst Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.10
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Horizon 2020 Framework Programme
- H2020 Marie Skłodowska-Curie Actions