Myosin-9b Controls Epithelial Brush Border Architecture through Motility-Dependent RhoA Signaling
Genetic variations in the MYO9B gene have been associated with Crohn's disease, celiac disease, and ulcerative colitis. These diseases have been characterized as primarily immune disorders. However, the overall molecular basis for the influence of Myo9b in these diseases remains poorly understood. Using in vivo small intestine ileum and human cell culture models, we identify a molecular function…
The MYO9B gene has been linked to conditions such as Crohn's disease, celiac disease, and ulcerative colitis. Despite these associations, the role of Myo9b in these diseases has been unclear. Through in vivo studies using small intestine ileum and human cell cultures, researchers have identified a specific function of Myo9b in shaping epithelial brush border microvilli.
Utilizing live-cell super-resolution microscopy, the team observed Myo9b's movement towards microvilli tips and its direct influence on small GTPase signaling via an active RhoA biosensor. In knockout cells, microvilli quantity and movement were disrupted, but microvilli remained intact with proper incorporation of membrane regulators like Ezrin.
Conversely, introducing the Myo9b-S1011A disease variant as the sole genetic copy in human cells led to a complete absence of microvilli and Ezrin localization at the apical region. These findings suggest that Myo9b plays a crucial role in epithelial cell morphology and microvilli formation. Moreover, the research implies that the S1011A variant may contribute to disease states through its impact on microvilli structure.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
