PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli.

Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for the F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule plays a role in controlling microvillar morphology.

IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and Independent Mechanisms.

Transporting epithelial cells like those that line the gut build large arrays of actin-supported protrusions called microvilli, which extend from the apical surface into luminal spaces to increase functional surface area. Although critical for maintaining physiological homeostasis, mechanisms controlling the formation of microvilli remain poorly understood. Here, we report that the inverse-bin-amphiphysin-Rvs (I-BAR)-domain-containing protein insulin receptor tyrosine kinase substrate (IRTKS) (also known as BAIAP2L1) promotes the growth of epithelial microvilli.

MyTH4-FERM myosins in the assembly and maintenance of actin-based protrusions.

Unconventional myosins are actin-based molecular motors that serve a multitude of roles within the cell. One group of myosin motors, the MyTH4-FERM myosins, play an integral part in building and maintaining finger-like protrusions, which allow cells to interact with their external environment. Suggested to act primarily as transporters, these motor proteins enrich adhesion molecules, actin-regulatory proteins and other factors at the tips of filopodia, microvilli, and stereocilia.

Impact of cordon-bleu expression on actin cytoskeleton architecture and dynamics.

Cordon-bleu (COBL) is a multifunctional WASP-Homology 2 (WH2) domain-containing protein implicated in a wide variety of cellular functions ranging from dendritic arborization in neurons to the assembly of microvilli on the surface of transporting epithelial cells. In vitro biochemical studies suggest that COBL is capable of nucleating and severing actin filaments, among other activities. How the multiple activities of COBL observed in vitro contribute to its function in cells remains unclear.

Cortactin promotes exosome secretion by controlling branched actin dynamics.

Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion.

ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation.

Transporting and sensory epithelial cells shape apical specializations using protocadherin-based adhesion. In the enterocyte brush border, protocadherin function requires a complex of cytoplasmic binding partners, although the composition of this complex and logic governing its assembly remain poorly understood. We found that ankyrin repeat and sterile α motif domain containing 4B (ANKS4B) localizes to the tips of adherent brush border microvilli and is essential for intermicrovillar adhesion.

Cordon bleu promotes the assembly of brush border microvilli.

Microvilli are actin-based protrusions found on the surface of diverse cell types, where they amplify membrane area and mediate interactions with the external environment. In the intestinal tract, these protrusions play central roles in nutrient absorption and host defense and are therefore essential for maintaining homeostasis. However, the mechanisms controlling microvillar assembly remain poorly understood.

Dynamics of brush border remodeling induced by enteropathogenic E. coli.

Enteropathogenic Escherichia coli (EPEC) induces dramatic remodeling of enterocyte brush borders, a process that includes microvillar effacement and actin pedestal formation. Although the Arp2/3 complex is involved in formation of a branched actin network within pedestals, the fate of parallel actin bundles in microvilli during infection remains unclear. Here, we find that in polarized intestinal epithelial cells, EPEC stimulates long-range microvillar dynamics, pulling protrusions toward sites of bacterial attachment in a process mediated by the adhesion molecule protocadherin-24.

Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion.

Transporting epithelial cells build apical microvilli to increase membrane surface area and enhance absorptive capacity. The intestinal brush border provides an elaborate example with tightly packed microvilli that function in nutrient absorption and host defense. Although the brush border is essential for physiological homeostasis, its assembly is poorly understood.

Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition.

Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protein interaction between blood vessel epicardial substance (Bves) and N-myc downstream regulated gene 4 (NDRG4) is critical for regulation of epicardial cell directional movement, as disruption of this interaction randomizes migratory patterns.