Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan Department of Molecular Medical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
J Cell Sci. 2015 Jul 1;128(13):2244-58. doi: 10.1242/jcs.160879. Epub 2015 May 14.
Epithelial apicobasal polarity has fundamental roles in epithelial physiology and morphogenesis. The PAR complex, comprising PAR-3, PAR-6 and atypical protein kinase C (aPKC), is involved in determining cell polarity in various biological contexts, including in epithelial cells. However, it is not fully understood how the PAR complex induces apicobasal polarity. In this study, we found that PAR-3 regulates the protein expression of Girdin (also known as GIV or CCDC88A), a guanine-nucleotide-exchange factor (GEF) for heterotrimeric Gαi subunits, at the transcriptional level by cooperating with the AP-2 transcription factor. In addition, we confirmed that PAR-3 physically interacts with Girdin, and show that Girdin, together with the Gαi3 (also known as GNAI3), controls tight junction formation, apical domain development and actin organization downstream of PAR-3. Taken together, our findings suggest that transcriptional upregulation of Girdin expression and Girdin-Gαi3 signaling play crucial roles in regulating epithelial apicobasal polarity through the PAR complex.
上皮细胞的顶底极性在其生理和形态发生中起着重要作用。PAR 复合物，包括 PAR-3、PAR-6 和非典型蛋白激酶 C（aPKC），参与了包括上皮细胞在内的各种生物学环境中细胞极性的确定。然而，PAR 复合物如何诱导顶底极性尚不完全清楚。在这项研究中，我们发现 PAR-3 通过与 AP-2 转录因子合作，在转录水平上调节 Girdin（也称为 GIV 或 CCDC88A）的蛋白表达，Girdin 是异三聚体 Gαi 亚基的鸟嘌呤核苷酸交换因子（GEF）。此外，我们证实 PAR-3 与 Girdin 有物理相互作用，并表明 Girdin 与 Gαi3（也称为 GNAI3）一起控制紧密连接的形成、顶端区域的发育和 PAR-3 下游的肌动蛋白组织。总之，我们的研究结果表明，Girdin 表达的转录上调和 Girdin-Gαi3 信号转导通过 PAR 复合物在上皮细胞顶底极性的调节中起着关键作用。
