The Drosophila Bcl-2 family member dBorg-1 functions in the apoptotic response to UV-irradiation

Abstract

As with all metazoans, the fly makes extensive use of selective programmed cell death (PCD) to remove excess cells and properly sculpt developing tissues. Several core components of the cell death machinery have been identified in flies, including caspases and an Apaf-1 ortholog [1] [2] [3] [4]. One missing component has been a member of the Bcl-2 family of proteins, which act either pro- or anti-apoptotically as upstream regulatory proteins. Here, we report the identification of Bcl-2 family members in Drosophila - dBorg-1 (Drosophila Bcl-2 ortholog), also identified by Igaki et al. [5], and dBorg-2. Removal of dBorg-1 function during Drosophila embryonic development resulted in excess glial cells, demonstrating its pro-apoptotic function. In cell culture assays, dBorg-1 efficiently induced apoptosis but, remarkably, also demonstrated protective activity when death stimuli were introduced. Finally, ectopic expression of dBorg-1 in the eye led to subtle defects that were strongly potentiated by ultra violet (UV) irradiation, resulting in a dramatic loss of retinal cells.

Molecular determinants of the subcellular localization of the Drosophila Bcl-2 homologues DEBCL and BUFFY

“…[1][2][3][4] In contrast, the Drosophila genome possesses only two Bcl-2 family members, DEBCL and BUFFY. [6][7][8][9][10][11] The functions of Bcl-2 family members in Drosophila remains enigmatic as the inhibitor of apoptosis protein DIAP1 is the main regulator of caspase activation in the fly. 20,21 DEBCL was initially characterized as a proapoptotic protein; however, there is evidence to suggest that it also has prosurvival function in response to some death insults.…”

“…20,21 DEBCL was initially characterized as a proapoptotic protein; however, there is evidence to suggest that it also has prosurvival function in response to some death insults. [6][7][8][9][10] Overexpression of BUFFY in Drosophila embryos can provide partial protection against radiation-induced apoptosis. 11 More recent data have attributed both prosurvival and proapoptotic functions to BUFFY.…”

“…5 There are two Bcl-2 family members in Drosophila, BUFFY and DEBCL, both of which are closely related to mammalian Bok and contain BH1-BH3 domains. [6][7][8][9][10][11] Unlike in mammals, BH1-BH4 prosurvival members of Bcl-2 and the BH3-only proteins have not been reported in Drosophila. Although the precise functions of the Drosophila Bcl-2 homologues are not understood, some data suggest that BUFFY and DEBCL may have context-dependent activities.…”

“…Although the precise functions of the Drosophila Bcl-2 homologues are not understood, some data suggest that BUFFY and DEBCL may have context-dependent activities. [6][7][8][9][10][11][12] While it is well established that DEBCL largely localizes to mitochondria, 7 the exact localization of BUFFY is not known. In this study, we show that BUFFY localizes primarily to endoplasmic reticula (ER).…”

“…Overexpression of DEBCL in cells and in transgenic flies induces apoptosis. [6][7][8][9] In transfected cells, the proapoptotic activity of DEBCL is dependent upon its MA-dependent mitochondrial localization. To assess the ability of BUFFY to induce cell death, full-length and DMA mutant were expressed in Drosophila BG2 cells together with a reporter plasmid (pIE-LacZ).…”