The apical extracellular matrix (aECM), organized by polarized epithelial cells, exhibits complex structures. The tectorial membrane (TM), an aECM in the cochlea mediating auditory transduction, exhibits highly ordered domain-specific architecture. α-Tectorin (TECTA), a glycosylphosphatidylinositol (GPI)-anchored ECM protein, is essential for TM organization. Here, we identified that α-tectorin is released by distinct modes: proteolytic shedding by TMPRSS2 and GPI-anchor-dependent release from the microvillus tip in mice. In the medial/limbal domain, proteolytically shed α-tectorin forms dense fibers. In contrast, in the lateral/body domain, where supporting cells exhibit dense microvilli, shedding restricts α-tectorin to the microvillus tip, compartmentalizing collagen-binding sites. Tip-localized α-tectorin is released in a GPI-anchor-dependent manner to form collagen-crosslinking fibers, maintaining the spacing and parallel organization of collagen fibrils. Overall, these distinct release modes of α-tectorin determine domain-specific organization, with the microvillus coordinating release modes along its membrane to assemble the higher-order ECM architecture.

中文翻译：

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微绒毛控制盖膜细胞外基质的形态发生


由极化上皮细胞组织的顶端细胞外基质 （aECM） 表现出复杂的结构。盖膜 （TM） 是耳蜗中介导听觉转导的 aECM，表现出高度有序的域特异性结构。α-Tectorin （TECTA） 是一种糖基磷脂酰肌醇 （GPI） 锚定的 ECM 蛋白，对 TM 组织至关重要。在这里，我们确定 α-tectorin 通过不同的模式释放：TMPRSS2 的蛋白水解脱落和小鼠微绒毛尖端的 GPI 锚依赖性释放。在内侧/角膜缘结构域中，蛋白水解脱落的 α-tectorin 形成致密的纤维。相比之下，在支持细胞表现出致密的微绒毛的外侧/身体结构域中，脱落将 α-tectorin 限制在微绒毛尖端，分隔胶原蛋白结合位点。尖端定位的 α-tectorin 以 GPI 锚依赖性方式释放，形成胶原交联纤维，维持胶原纤维的间距和平行组织。总体而言，α-tectorin 的这些不同释放模式决定了结构域特异性组织，微绒毛沿其膜协调释放模式以组装更高阶的 ECM 结构。