Molecular model of the microvillar cytoskeleton and organization of the brush border

• Published in: PloS one Vol. 5; no. 2; p. e9406
• Main Authors: Brown, Jeffrey W, McKnight, C James
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.02.2010; Public Library of Science (PLoS)
• Subjects: Absorptivity; Actin; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - metabolism; Actins - chemistry; Actins - metabolism; Analysis; Animals; Biochemistry/Macromolecular Assemblies and Machines; Bioinformatics; Biophysics; Biophysics/Theory and Simulation; Brushes; Calcium binding proteins; Calcium-binding protein; Calmodulin; Calmodulin - chemistry; Calmodulin - metabolism; Cell Biology/Morphogenesis and Cell Biology; Cellular structure; Crosslinking; Crystallization; Crystallography; Crystals; Cytoskeleton; Cytoskeleton - chemistry; Cytoskeleton - metabolism; Deformation; Deformation mechanisms; Epithelial cells; Fimbrin; Gastroenterology and Hepatology/Small Intestine; Geometry; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Membrane proteins; Microfilament Proteins - chemistry; Microfilament Proteins - metabolism; Microscopy; Microvilli - metabolism; Microvillus; Models, Molecular; Morphogenesis; Morphology; Myosin; Myosins - chemistry; Myosins - metabolism; Pathogens; Physiology; Protein Conformation; Protein turnover; Proteins; Spectrin; Spectrin - chemistry; Spectrin - metabolism; Surface chemistry; Symmetry; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009406

Brush border microvilli are approximately 1-microm long finger-like projections emanating from the apical surfaces of certain, specialized absorptive epithelial cells. A highly symmetric hexagonal array of thousands of these uniformly sized structures form the brush border, which in addition to aiding in nutrient absorption also defends the large surface area against pathogens. Here, we present a molecular model of the protein cytoskeleton responsible for this dramatic cellular morphology. The model is constructed from published crystallographic and microscopic structures reported by several groups over the last 30+ years. Our efforts resulted in a single, unique, self-consistent arrangement of actin, fimbrin, villin, brush border myosin (Myo1A), calmodulin, and brush border spectrin. The central actin core bundle that supports the microvillus is nearly saturated with fimbrin and villin cross-linkers and has a density similar to that found in protein crystals. The proposed model accounts for all major proteinaceous components, reproduces the experimentally determined stoichiometry, and is consistent with the size and morphology of the biological brush border membrane. The model presented here will serve as a structural framework to explain many of the dynamic cellular processes occurring over several time scales, such as protein diffusion, association, and turnover, lipid raft sorting, membrane deformation, cytoskeletal-membrane interactions, and even effacement of the brush border by invading pathogens. In addition, this model provides a structural basis for evaluating the equilibrium processes that result in the uniform size and structure of the highly dynamic microvilli.