Su(dx) E3 ubiquitin ligase-dependent and -independent functions of polychaetoid, the Drosophila ZO-1 homologue.

Su(dx) E3 ubiquitin ligase-dependent and -independent functions of polychaetoid, the Drosophila ZO-1 homologue.
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DOI:
10.1083/jcb.201007023
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发表时间:
2011-01-10
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Baron M
Baron M
中科院分区:
其他
文献类型:
--
作者:
Djiane A;Shimizu H;Wilkin M;Mazleyrat S;Jennings MD;Avis J;Bray S;Baron M

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多毛体与粘附体连接组织协调受体运输和信号。闭塞带(ZO)蛋白是定位于细胞连接处的分子支架,在哺乳动物中调节上皮的完整性。利用新产生的零等位基因,我们证明了多毛囊样蛋白(polychaetoid, pyd)是果蝇ZO的独特同源物,可以调节粘附体连接定位受体(如Notch)的积累,尽管它在上皮极化中是必不可少的。Pyd在感觉器官发育过程中正调控Notch信号通路,而负调控Notch通路限制卵巢种系干细胞生态位。在这两种情况下,我们发现Pyd与WW结构域E3泛素连接酶Su(dx)之间存在核心拮抗相互作用。Pyd直接结合Su(dx),部分通过非规范的w -结合基序。Pyd还限制上皮翅膀细胞的数量来控制成年翅膀的形状,这一功能与FERM蛋白扩增有关,不依赖于Su(dx)。由于Su(dx)和Expanded都调节转运,我们认为ZO蛋白的保守作用是协调受体转运和连接组织的信号传导。
Polychaetoid coordinates receptor trafficking and signaling with adherens junction organization. Zona occludens (ZO) proteins are molecular scaffolds localized to cell junctions, which regulate epithelial integrity in mammals. Using newly generated null alleles, we demonstrate that polychaetoid (pyd), the unique Drosophila melanogaster ZO homologue, regulates accumulation of adherens junction–localized receptors, such as Notch, although it is dispensable for epithelial polarization. Pyd positively regulates Notch signaling during sensory organ development but acts negatively on Notch to restrict the ovary germline stem cell niche. In both contexts, we identify a core antagonistic interaction between Pyd and the WW domain E3 ubiquitin ligase Su(dx). Pyd binds Su(dx) directly, in part through a noncanonical WW-binding motif. Pyd also restricts epithelial wing cell numbers to control adult wing shape, a function associated with the FERM protein Expanded and independent of Su(dx). As both Su(dx) and Expanded regulate trafficking, we propose that a conserved role of ZO proteins is to coordinate receptor trafficking and signaling with junctional organization.
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