顶端整合素是调节上皮屏障的可切换目标。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI:10.1242/jcs.263580
Raven J Peterson, Ryan C Reed, Colin R Zamecnik, Marwa A Sallam, Joel A Finbloom, Francisco J Martinez, Joshua M Levy, Aekkacha Moonwiriyakit, Tejal A Desai, Michael Koval
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引用次数: 0

摘要

紧密连接调节上皮屏障功能,并已证明受到多种蛋白质的影响。顶端整合素已被确定为上皮屏障功能的潜在调控因子,但目前只有间接的方法用于测量整合素对上皮屏障的调控。在这里,我们使用与抗整合素β1抗体结合的聚合物纳米线,特异性地靶向封闭或开放构象的顶端定位整合素。研究发现,顶端整合素对屏障的调节具有构象特异性。以封闭构象整合素为靶的纳米线增加了上皮细胞的通透性,并使闭锁带-1(ZO-1)从线性形态变为皱褶形态。Claudin-2和claudin-4与ZO-1共定位,也呈皱褶状,但claudin-1和claudin-7仍呈线状。褶皱依赖于肌球蛋白轻链(MLCK)和 Rho 激酶(ROCK)。相反,以开放构象的整合素为靶标会降低上皮的通透性,并使连接更加线性化。抗整合素β1纳米线对肌动蛋白和滑蛋白的影响各不相同,这取决于它们是否含有激活或抑制抗体。因此,顶端整合素可作为一种构象敏感开关,调节上皮屏障功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Apical integrins as a switchable target to regulate the epithelial barrier.

Tight junctions regulate epithelial barrier function and have been shown to be influenced by multiple classes of proteins. Apical integrins have been identified as potential regulators of epithelial barrier function; however, only indirect approaches have been used to measure integrin regulation of the epithelial barrier. Here, we used polymeric nanowires conjugated with anti-integrin β1 antibodies to specifically target apically localized integrins in either their closed or open conformation. Barrier regulation by apical integrins was found to be conformation specific. Nanowires targeting integrins in the closed conformation increased epithelial permeability and caused zonula occludens-1 (ZO-1, also known as TJP1) to change from a linear to a ruffled morphology. Claudin-2 and claudin-4 colocalized with ZO-1 and were also ruffled; however, claudin-1 and claudin-7 remained linear. Ruffling was dependent on myosin light chain kinases (MLCKs) and Rho kinases (ROCKs). Conversely, targeting integrins in the open conformation decreased epithelial permeability and made junctions more linearized. Anti-integrin β1 nanowires differentially affected actin and talin (analyzed using pan-talin antibodies), depending on whether they contained activating or inhibitory antibodies. Thus, apical integrins can act as a conformation-sensitive switch that regulates epithelial barrier function.

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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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