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Intestinal Brush Border Assembly Driven by Protocadherin-Based Intermicrovillar Adhesion

Authors
 Scott W. Crawley  ;  David A. Shifrin Jr.  ;  Nathan E. Grega-Larson  ;  Russell E. McConnell  ;  Andrew E. Benesh  ;  Suli Mao  ;  Yuxi Zheng  ;  Qing Yin Zheng  ;  Ki Taek Nam  ;  Bryan A. Millis  ;  Bechara Kachar  ;  Matthew J. Tyska 
Citation
 CELL, Vol.157(2) : 433-446, 2014 
Journal Title
 CELL 
ISSN
 0092-8674 
Issue Date
2014
MeSH
Animals ; COS Cells ; Caco-2 Cells ; Cadherins/metabolism* ; Calcium/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cercopithecus aethiops ; Disease Models, Animal ; Enterocytes/cytology ; Enterocytes/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Microvilli/metabolism* ; Microvilli/ultrastructure ; Myosins/metabolism ; Usher Syndromes/pathology
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0092867414002153
DOI
10.1016/j.cell.2014.01.067
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98799
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