Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion

Scott W. Crawley, David A. Shifrin, Nathan E. Grega-Larson, Russell E. McConnell, Andrew E. Benesh, Suli Mao, Yuxi Zheng, Qing Yin Zheng, KiTaek Nam, Bryan A. Millis, Bechara Kachar, Matthew J. Tyska

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 Ca2+-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

Original languageEnglish
Pages (from-to)433-446
Number of pages14
JournalCell
Volume157
Issue number2
DOIs
Publication statusPublished - 2014 Apr 10

Fingerprint

Brushes
Microvilli
Adhesion
Usher Syndromes
Mucins
Pathology
Myosins
Nutrients
Membranes
Defects
Homeostasis
Epithelial Cells
Proteins
Food

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Crawley, S. W., Shifrin, D. A., Grega-Larson, N. E., McConnell, R. E., Benesh, A. E., Mao, S., ... Tyska, M. J. (2014). Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell, 157(2), 433-446. https://doi.org/10.1016/j.cell.2014.01.067
Crawley, Scott W. ; Shifrin, David A. ; Grega-Larson, Nathan E. ; McConnell, Russell E. ; Benesh, Andrew E. ; Mao, Suli ; Zheng, Yuxi ; Zheng, Qing Yin ; Nam, KiTaek ; Millis, Bryan A. ; Kachar, Bechara ; Tyska, Matthew J. / Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. In: Cell. 2014 ; Vol. 157, No. 2. pp. 433-446.
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Crawley, SW, Shifrin, DA, Grega-Larson, NE, McConnell, RE, Benesh, AE, Mao, S, Zheng, Y, Zheng, QY, Nam, K, Millis, BA, Kachar, B & Tyska, MJ 2014, 'Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion', Cell, vol. 157, no. 2, pp. 433-446. https://doi.org/10.1016/j.cell.2014.01.067

Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. / Crawley, Scott W.; Shifrin, David A.; Grega-Larson, Nathan E.; McConnell, Russell E.; Benesh, Andrew E.; Mao, Suli; Zheng, Yuxi; Zheng, Qing Yin; Nam, KiTaek; Millis, Bryan A.; Kachar, Bechara; Tyska, Matthew J.

In: Cell, Vol. 157, No. 2, 10.04.2014, p. 433-446.

Research output: Contribution to journalArticle

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Crawley SW, Shifrin DA, Grega-Larson NE, McConnell RE, Benesh AE, Mao S et al. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell. 2014 Apr 10;157(2):433-446. https://doi.org/10.1016/j.cell.2014.01.067