Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan.
FEBS J. 2013 Jan;280(2):476-88. doi: 10.1111/j.1742-4658.2012.08696.x. Epub 2012 Jul 26.
To date our understanding of Drosophila receptor protein tyrosine phosphatases (R-PTPs) in the regulation of signal transduction is limited. Of the seven R-PTPs identified in flies, six are involved in the axon guidance that occurs during embryogenesis. However, whether and how R-PTPs may control key steps of Drosophila development is not clear. In this study we investigated the potential role of Drosophila R-PTPs in developmental processes outside the neuronal system and beyond the embryogenesis stage. Through systematic data mining of available microarray databases, we found the mRNA level of PTP52F to be highly enriched in the midgut of flies at the larva-pupa transition. This finding was confirmed by gut tissue staining with a specific antibody. The unique spatiotemporal expression of PTP52F suggests that it is possibly involved in regulating metamorphosis during the transformation from larva to pupa. To test this hypothesis, we employed RNA interference to examine the defects of transgenic flies. We found that ablation of endogenous PTP52F led to high lethality characterized by the pharate adult phenotype, occurring due to post pupal eclosion failure. These results show that PTP52F plays an indispensable role during the larva-pupa transition. We also found that PTP52F could be reclassified as a member of the subtype R3 PTPs instead of as an unclassified R-PTP without a human ortholog, as suggested previously. Together, these findings suggest that Drosophila R-PTPs may control metamorphosis and other biological processes beyond our current knowledge.
迄今为止,我们对果蝇受体蛋白酪氨酸磷酸酶(R-PTPs)在信号转导调控中的了解还很有限。在已鉴定的 7 种果蝇 R-PTP 中,有 6 种参与胚胎发生过程中的轴突导向。然而,R-PTP 是否以及如何控制果蝇发育的关键步骤尚不清楚。在这项研究中,我们研究了果蝇 R-PTPs 在神经元系统之外和胚胎发生阶段之外的发育过程中的潜在作用。通过对现有微阵列数据库进行系统的数据挖掘,我们发现 PTP52F 的 mRNA 水平在幼虫到蛹过渡期间的果蝇中高度富集在中肠。这一发现通过特异性抗体对肠道组织的染色得到了证实。PTP52F 的独特时空表达表明,它可能参与调节从幼虫到蛹的变态过程。为了验证这一假说,我们采用 RNA 干扰技术来检查转基因果蝇的缺陷。我们发现,内源性 PTP52F 的缺失导致高致死率,表现为拟蛹成虫表型,这是由于蛹后羽化失败所致。这些结果表明 PTP52F 在幼虫到蛹的过渡过程中起着不可或缺的作用。我们还发现,PTP52F 可以重新归类为 R3 PTPs 亚类成员,而不是以前没有人类同源物的未分类 R-PTP。总之,这些发现表明,果蝇 R-PTPs 可能控制着变态和其他超出我们目前认知的生物学过程。