Runx1 mediates the development of the granular convoluted tubules in the submandibular glands.
Runx1 mediates the development of the granular convoluted tubules in the submandibular glands.
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DOI：
10.1371/journal.pone.0184395
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Yamashiro T
中科院分区：
文献类型：
--
作者：
Ono Minagi H;Sarper SE;Kurosaka H;Kuremoto KI;Taniuchi I;Sakai T;Yamashiro T
小鼠颗粒曲管（GCT），这是唯一位于下颌下腺（SMG）已知的发展和维持其结构的雄激素依赖性的方式。我们以前证明GCT是由核心结合因子β（CBFβ）的上皮缺失引起的，CBF β是一种与任何Runt相关转录因子（RUNX）蛋白（RUNX 1，2和3）物理相互作用的转录因子。该结果清楚地表明Runx /Cbfb信号通路在GCT的发展中是不可或缺的。然而，目前尚不清楚哪种RUNX蛋白通过激活Runx /Cbfb信号通路在GCT的发展中发挥有用的作用。过去的研究表明，Runx /Cbfb信号通路在发育和稳态事件的各个方面发挥重要作用。此外，Runx基因具有不同的时空要求，这取决于生物学情况。在本研究中，SMG的GCT在上皮特异性Runx 1条件性基因敲除（cKO）小鼠中显示出显著的表型，其表型模仿了Cbfb的上皮缺失。结果表明，Runx 1在GCT的开发过程中是Cbfb的合作伙伴。我们还发现Runx 1的缺失导致雄性小鼠唾液分泌减少。与这一发现一致的是，水通道之一，水通道蛋白-5（AQP 5）在Runx 1突变体的细胞质中被错误定位，这表明Runx 1在AQP 5的膜运输中具有新的作用。总之，目前的研究结果表明，RUNX 1是必不可少的GCT的发展。此外，RUNX 1还可能参与SMG中腺泡细胞的AQP 5蛋白的膜运输，以允许唾液的适当分泌。
The mouse granular convoluted tubules (GCTs), which are only located in the submandibular gland (SMG) are known to develop and maintain their structure in an androgen-dependent manner. We previously demonstrated that the GCTs are involuted by the epithelial deletion of core binding factor β (CBFβ), a transcription factor that physically interacts with any of the Runt-related transcription factor (RUNX) proteins (RUNX1, 2 and 3). This result clearly demonstrates that the Runx /Cbfb signaling pathway is indispensable in the development of the GCTs. However, it is not clear which of the RUNX proteins plays useful role in the development of the GCTs by activating the Runx /Cbfb signaling pathway. Past studies have revealed that the Runx /Cbfb signaling pathway plays important roles in various aspects of development and homeostatic events. Moreover, the Runx genes have different temporospatial requirements depending on the biological situation. In the present study, the GCTs of the SMG showed a remarkable phenotype of, which phenocopied the epithelial deletion of Cbfb, in epithelial-specific Runx1 conditional knock-out (cKO) mice. The results indicate that Runx1 works as a partner of Cbfb during the development of the GCTs. We also discovered that the depletion of Runx1 resulted in the reduced secretion of saliva in male mice. Consistent with this finding, one of the water channels, Aquaporin-5 (AQP5) was mislocalized in the cytoplasm of the Runx1 mutants, suggesting a novel role of Runx1 in the membrane trafficking of AQP5. In summary, the present findings demonstrated that RUNX1 is essential for the development of the GCTs. Furthermore, RUNX1 could also be involved in the membrane trafficking of the AQP5 protein of the acinar cells in the SMG in order to allow for the proper secretion of saliva.