2. Academic Validation
  3. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion

Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion

  • Cell. 2014 Apr 10;157(2):433-446. doi: 10.1016/j.cell.2014.01.067.
Scott W Crawley 1,  David A Shifrin Jr 1,  Nathan E Grega-Larson 1,  Russell E McConnell 1,  Andrew E Benesh 1,  Suli Mao 1,  Yuxi Zheng 2,  Qing Yin Zheng 2,  Ki Taek Nam 3,  Bryan A Millis 4,  Bechara Kachar 4,  Matthew J Tyska 5
Affiliations

Affiliations

  • 1 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 2 Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 3 Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.
  • 4 National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
  • 5 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: [email protected].
PMID: 24725409 DOI: 10.1016/j.cell.2014.01.067
Abstract

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:

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