Grieder Nicole C, Caussinus Emmanuel, Parker David S, Cadigan Kenneth, Affolter Markus, Luschnig Stefan
Abteilung Zellbiologie, Biozentrum der Universität Basel, Basel, Switzerland.
PLoS One. 2008 Sep 19;3(9):e3241. doi: 10.1371/journal.pone.0003241.
There is increasing evidence that tissue-specific modifications of basic cellular functions play an important role in development and disease. To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the gammaCOP gene, which encodes a subunit of the COPI coatomer complex.
We found that gammaCOP is essential for the viability of the Drosophila embryo. In the absence of zygotic gammaCOP activity, embryos die late in embryogenesis and display pronounced defects in morphogenesis of the embryonic epidermis and of tracheal tubes. The coordinated cell rearrangements and cell shape changes during tracheal tube morphogenesis critically depend on apical secretion of certain proteins. Investigation of tracheal morphogenesis in gammaCOP loss-of-function mutants revealed that several key proteins required for tracheal morphogenesis are not properly secreted into the apical lumen. As a consequence, gammaCOP mutants show defects in cell rearrangements during branch elongation, in tube dilation, as well as in tube fusion. We present genetic evidence that a specific subset of the tracheal defects in gammaCOP mutants is due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we identified a critical target protein of COPI-dependent secretion in epithelial tube morphogenesis.
CONCLUSIONS/SIGNIFICANCE: These studies highlight the role of COPI coatomer-mediated vesicle trafficking in both general and tissue-specific secretion in a multicellular organism. Although COPI coatomer is generally required for protein secretion, we show that the phenotypic effect of gammaCOP mutations is surprisingly specific. Importantly, we attribute a distinct aspect of the gammaCOP phenotype to the effect on a specific key target protein.
越来越多的证据表明，基本细胞功能的组织特异性修饰在发育和疾病中起着重要作用。为了确定COPI衣被蛋白介导的膜运输在果蝇发育中的功能，我们旨在在γCOP基因中创建功能缺失突变，该基因编码COPI衣被蛋白复合物的一个亚基。
我们发现γCOP对果蝇胚胎的生存能力至关重要。在没有合子γCOP活性的情况下，胚胎在胚胎发育后期死亡，并在胚胎表皮和气管的形态发生中表现出明显的缺陷。气管形态发生过程中协调的细胞重排和细胞形状变化严重依赖于某些蛋白质的顶端分泌。对γCOP功能缺失突变体中气管形态发生的研究表明，气管形态发生所需的几种关键蛋白质没有正确分泌到顶端管腔中。因此，γCOP突变体在分支伸长、管扩张以及管融合过程中的细胞重排方面表现出缺陷。我们提供了遗传学证据，表明γCOP突变体中气管缺陷的一个特定子集是由于透明带蛋白Piopio的分泌减少所致。因此，我们确定了上皮管形态发生中COPI依赖性分泌的一个关键靶蛋白。
结论/意义：这些研究突出了COPI衣被蛋白介导的囊泡运输在多细胞生物的一般和组织特异性分泌中的作用。虽然COPI衣被蛋白通常是蛋白质分泌所必需的，但我们表明γCOP突变的表型效应出人意料地具有特异性。重要的是，我们将γCOP表型的一个独特方面归因于对特定关键靶蛋白的影响。
