Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants.
Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants.
复制标题
果蝇蛇皮突变体中连接完整性受损表型与年龄相关的肾功能障碍。
DOI：
10.1242/jcs.261118
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发表时间：
2023-10-01
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
转运上皮细胞提供了抵抗病原性损伤的保护屏障，同时允许离子、溶质和水与外部环境的受控交换。在无脊椎动物中，这些功能依赖于“紧密”分隔连接（SJS）的形成和维持。然而，SJS影响运输能力和组织稳态的机制，以及这些是如何通过老化来调节的，仍然没有完全了解。在这里，我们证明了果蝇肾（Malpighian）小管经历了年龄依赖性的分泌能力下降，这与SJ蛋白的错误定位和细胞形态和组织稳态的进行性退化。急性损失的SJ蛋白蛇皮在成人肾小管诱导细胞和组织结构的渐进性变化，包括改变表达和定位的连接蛋白与细胞极性和屏障完整性的损失伴随，证明了受损的连接完整性是足以复制这些衰老相关的表型。总之，我们的工作证明了上皮屏障完整性，小管运输能力，肾脏稳态和生物体活力之间的重要联系，以及对衰老和肾脏疾病的基础机制提供了新的见解。总结：在果蝇中，与年龄相关的肾功能下降是由于上皮屏障完整性的丧失和液体稳态的失败，通过细胞特异性敲低必需的连接蛋白蛇皮的作用表型模拟。
Transporting epithelia provide a protective barrier against pathogenic insults while allowing the controlled exchange of ions, solutes and water with the external environment. In invertebrates, these functions depend on formation and maintenance of ‘tight’ septate junctions (SJs). However, the mechanism by which SJs affect transport competence and tissue homeostasis, and how these are modulated by ageing, remain incompletely understood. Here, we demonstrate that the Drosophila renal (Malpighian) tubules undergo an age-dependent decline in secretory capacity, which correlates with mislocalisation of SJ proteins and progressive degeneration in cellular morphology and tissue homeostasis. Acute loss of the SJ protein Snakeskin in adult tubules induced progressive changes in cellular and tissue architecture, including altered expression and localisation of junctional proteins with concomitant loss of cell polarity and barrier integrity, demonstrating that compromised junctional integrity is sufficient to replicate these ageing-related phenotypes. Taken together, our work demonstrates a crucial link between epithelial barrier integrity, tubule transport competence, renal homeostasis and organismal viability, as well as providing novel insights into the mechanisms underpinning ageing and renal disease. Summary: In Drosophila, age-related decreased kidney function is due to loss of epithelial barrier integrity and failure of fluid homeostasis, effects phenocopied by cell-specific knockdown of the essential junctional protein Snakeskin.
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DOI：
10.1242/dev.088989
发表时间：
2013-03
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Denholm B;Hu N;Fauquier T;Caubit X;Fasano L;Skaer H
通讯作者：
Skaer H
影响因子：
8.8
作者：
Clark RI;Salazar A;Yamada R;Fitz-Gibbon S;Morselli M;Alcaraz J;Rana A;Rera M;Pellegrini M;Ja WW;Walker DW
通讯作者：
Walker DW
影响因子：
9.2
作者：
Denholm, B;Sudarsan, V;Skaer, H
通讯作者：
Skaer, H
影响因子：
2.6
作者：
Campbell, Kyra;Casanova, Jordi;Skaer, Helen
通讯作者：
Skaer, Helen
影响因子：
4.6
作者：
Bonello, Teresa T.;Choi, Wangsun;Peifer, Mark
通讯作者：
Peifer, Mark