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


RESULTS
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.


CONCLUSIONS
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.
Brown
Jeffrey W
JW
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
McKnight
C James
CJ
D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D003599:Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008958:Models, Molecular; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D002147:Calmodulin; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin; C026615:villin; D013049:Spectrin; D009218:Myosins