Myosin 1b regulates intestinal epithelial morphogenesis via interaction with UNC45A
Céline Revenu,
Corinne Lebreton,
Magda Cannata Serio,
Marion Rosello,
Rémi Duclaux-Loras,
Karine Duroure,
Ophélie Nicolle,
Fanny Eggeler,
Marie-Thérèse Prospéri,
Julie Stoufflet,
Juliette Vougny,
Priscilla Lépine,
Grégoire Michaux,
Nadine Cerf-Bensussan,
Evelyne Coudrier,
Franck Perez,
Marianna Parlato,
Filippo Del Bene
Affiliations
Céline Revenu
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France
Corinne Lebreton
INSERM, UMR1163, Laboratory of Intestinal Immunity and Institut Imagine, 75015 Paris, France
Magda Cannata Serio
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR 144, Paris, France
Marion Rosello
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France
Rémi Duclaux-Loras
INSERM, UMR1163, Laboratory of Intestinal Immunity and Institut Imagine, 75015 Paris, France
Karine Duroure
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France
Ophélie Nicolle
Université de Rennes, CNRS, IGDR (Institut de Génétique et de Développement de Rennes), UMR 6290, 35000 Rennes, France
Fanny Eggeler
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France
Marie-Thérèse Prospéri
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR 144, Paris, France
Julie Stoufflet
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France
Juliette Vougny
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France
Priscilla Lépine
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR 144, Paris, France
Grégoire Michaux
Université de Rennes, CNRS, IGDR (Institut de Génétique et de Développement de Rennes), UMR 6290, 35000 Rennes, France
Nadine Cerf-Bensussan
INSERM, UMR1163, Laboratory of Intestinal Immunity and Institut Imagine, 75015 Paris, France
Evelyne Coudrier
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR 144, Paris, France
Franck Perez
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR 144, Paris, France
Marianna Parlato
INSERM, UMR1163, Laboratory of Intestinal Immunity and Institut Imagine, 75015 Paris, France; Corresponding author
Filippo Del Bene
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris Cedex, France; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France; Corresponding author
Summary: 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.
