Role of Drosophila metalloprotease Sol narae in cell survival and its relationship with Dynein heavy chain 64C

Abstract

Part I Cell survival is essential for all living organisms to cope against multiple environmental insults, and the underlying mechanism is under intense investigation. It has been reported that cell signaling between dying cells and the surviving cells during apoptosis is essential for compensatory proliferation to prevent tissue loss. Here, we show that a Drosophila ADAMTS, sol narae (sona), is essential for sending signal to direct the cell division of the neighboring cells upon $\gamma$-irradiation. We have recently reported that Sona promotes Wg signaling by generating an active carboxyl terminal domain of Wg, Wg-CTD. We found that Sona is important for cell survival and blocking cell death. The cells with the high level of sona transcription were resistant to irradiation even without any Drosophila Inhibitor of Apoptosis 1 (DIAP1). Sona- and DIAP1-expressing cells were generally exclusive, and this exclusivity was increased upon $\gamma$-irradiation, indicating transcriptional regulation of sona and diap1 occurs coordinately in two opposite directions. Interestingly, these high-sona expressing cells were not dividing unlike the neighboring cells after irradiation. Furthermore, Wg-CTD could increase the transcriptional level of DIAP1 and cell division in a cell non-autonomous manner. Taken together, we propose that sona-expressing cells play essential roles as a signaling center and send out Wg-CTD, which then diffuses and turns on the transcription of genes for cell survival such as diap1 in Wg-responding cells.

Part II Metalloproteases are enzymes that play an important role in many biological processes such as cell proliferation, differentiation, migration, tissue remodeling and processing of growth factors. We have identified novel metalloprotease, sol narae, which has a disintergrin and metalloprotease domain homologous to those of ADAMTS family. To understand the function of Sona, we carried out genetic screen that suppresses Sona overexpression lethality phenotype. One of the suppressors was identified as Dynein heavy chain64C (Dhc64C) gene, which encodes a subunit of Dynein motor protein. Dynein carries cargos such as transcripts and vesicles toward the minus end of microtubules and known to be involved in endocytosis, and regulating apico-basal polarity. Our results show that loss of Dh64C results in cell death and increase in the level of Wg. Previous studies on Sona show that Sona is important for cell survival as well as promoting Wingless signaling. Based on these results, future studies on relationship between sona and Dhc64C in Wingless signaling is greatly needed.