Non-muscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli
- PMID: 33026933 [PubMed].
Brush border microvilli enable functions that are critical for epithelial homeostasis, including solute uptake and host defense. However, mechanisms that regulate the assembly and morphology of these protrusions are poorly understood. The parallel actin bundles that support microvilli have their pointed-end rootlets anchored in a filamentous meshwork referred to as the “terminal web.” Although classic EM studies revealed complex ultrastructure, the composition and function of the terminal web remains unclear. Here we identify non-muscle myosin-2C (NM2C) as a component of the terminal web. NM2C is found in a dense, isotropic layer of puncta across the sub-apical domain, which transects the rootlets of microvillar actin bundles. Puncta are separated by ∼210 nm, the expected size of filaments formed by NM2C. In intestinal organoid cultures, the terminal web NM2C network is highly dynamic and exhibits continuous remodeling. Using pharmacological and genetic perturbations in cultured intestinal epithelial cells, we found that NM2C controls the length of growing microvilli by regulating actin turnover in a manner that requires a fully active motor domain. Our findings answer a decades old question on the function of terminal web myosin and hold broad implications for understanding apical morphogenesis in diverse epithelial systems. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].