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

Autor:	Crawley SW; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Shifrin DA Jr; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Grega-Larson NE; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., McConnell RE; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Benesh AE; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Mao S; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Zheng Y; Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA., Zheng QY; Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA., Nam KT; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea., Millis BA; National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA., Kachar B; National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA., Tyska MJ; Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: matthew.tyska@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2014 Apr 10; Vol. 157 (2), pp. 433-446.
DOI:	10.1016/j.cell.2014.01.067
Abstrakt:	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.)
Databáze:	MEDLINE
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