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

Crawley SW, Shifrin DA, Grega-Larson NE, McConnell RE, Benesh AE, Mao S, Zheng Y, Zheng QY, Nam KT, Millis BA, Kachar B, Tyska MJ
Cell. 2014 157 (2): 433-446

PMID: 24725409 · PMCID: PMC3992856 · DOI:10.1016/j.cell.2014.01.067

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. We found that brush border assembly is driven by the formation of Ca(2+)-dependent adhesion links between adjacent microvilli. Intermicrovillar links are composed of protocadherin-24 and mucin-like protocadherin, which target to microvillar tips and interact to form a trans-heterophilic complex. The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips. Finally, a mouse model of Usher syndrome lacking harmonin exhibits microvillar protocadherin mislocalization and severe defects in brush border morphology. These data reveal an adhesion-based mechanism for brush border assembly and illuminate the basis of intestinal pathology in patients with Usher syndrome. PAPERFLICK:

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Caco-2 Cells Cadherins Calcium Carrier Proteins Chlorocebus aethiops COS Cells Cytoskeletal Proteins Disease Models, Animal Enterocytes HEK293 Cells Humans Mice Mice, Knockout Microvilli Myosins Usher Syndromes

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