Loss of intermicrovillar adhesion factor CDHR2 impairs basolateral junctional complexes in transporting epithelia.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2024-11-01 Epub Date: 2024-09-18 DOI:10.1091/mbc.E24-03-0113
Caroline S Cencer, Kianna L Robinson, Matthew J Tyska
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Abstract

Transporting epithelial cells in the gut and kidney rely on protocadherin-based apical adhesion complexes to organize microvilli that extend into luminal space. In these systems, CDHR2 and CDHR5 localize to the distal ends of microvilli, where they form an intermicrovillar adhesion complex (IMAC) that links the tips of these structures, promotes the formation of a well-ordered array of protrusions, and thus maximizes apical membrane surface area. Recently, we discovered that IMACs can also form between microvilli that extend from neighboring cells, across cell-cell junctions. As an additional point of physical contact between cells, transjunctional IMACs are well positioned to impact the integrity of canonical tight and adherens junctions that form more basolaterally. To begin to test this idea, we examined cell culture and mouse models that lacked CDHR2 expression and were unable to form IMACs. CDHR2 knockout perturbed cell and junction morphology, reduced key components from tight and adherens junctions, impaired barrier function, and increased the motility of single cells within established monolayers. These results support the hypothesis that, in addition to organizing apical microvilli, IMACs provide a layer of cell-cell contact that functions in parallel with canonical tight and adherens junctions to promote epithelial functions.

失去微绒毛间粘附因子 CDHR2 会损害运输上皮的基底侧连接复合体。
肠道和肾脏中的运输上皮细胞依靠基于原粘连蛋白的顶端粘附复合物来组织延伸到管腔空间的微绒毛。在这些系统中,CDHR2 和 CDHR5 定位于微绒毛的远端,它们在那里形成微绒毛间粘附复合物(IMAC),将这些结构的顶端连接起来,促进形成有序的突起阵列,从而使顶端膜表面积最大化。最近,我们发现 IMAC 还能在从相邻细胞延伸出来的微绒毛之间形成,跨越细胞-细胞连接点。作为细胞间的另一个物理接触点,跨功能 IMAC 具有良好的定位,可以影响在基底形成的典型紧密连接和粘连连接的完整性。为了开始验证这一观点,我们研究了缺乏 CDHR2 表达且无法形成 IMAC 的细胞培养和小鼠模型。CDHR2 基因敲除扰乱了细胞和连接形态,减少了紧密连接和粘连连接的关键成分,损害了屏障功能,并增加了单层细胞的运动性。这些结果支持了这样的假设:除了组织顶端微绒毛外,IMACs 还提供了一层细胞-细胞接触层,与典型的紧密连接和粘附连接并行发挥作用,促进上皮功能。[媒体:见正文]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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