Caspase-3/Drice as a critical regulator of actin dynamics through its dual control of small RhoGTPase family and Gelsolin in the Malpighian tubules of Drosophila.

Abstract

Caspases are executioner enzymes primarily known for their role in driving programmed cell death. However, they are now also known to regulate plethora of non-apoptotic functions such as proliferation, differentiation, endocytic trafficking, cell polarity, morphogenesis, inflammatory response and immune response. Here, in this study we report the role of Drosophila caspase 3, Drice, in spatial and dynamic regulation of actin filaments during development and proper functioning of the Malpighian tubules (MTs) of Drosophila melanogaster. Previously, we showed that Drice is crucial for the morphogenesis of the MTs, and its absence results in erroneous RhoGTPase signaling driving disarray in actin organization, this led to the formation of multiple fluid filled cysts in tubules. In the present study, we show that altered expression of two member of the Rho family of small GTPases, Rho1 and CDC42, perturbs the downstream signaling cascade. Reduced expression of Rok aborts the Rho1 signaling in Drice null mutants, whereas enhanced expression of CDC42 results in Arp2/3-driven hyper-polymerization of actin filaments. We compared Rho-GTPase interacting partners in Oregon R+ (Control) and Drice mutants, and identified the absence of Gelsolin-Rho1 interaction in Drice mutants. Moreover, its expression was significantly downregulated, in the MTs. These factors collectively influence the F-actin to G-actin ratio, which significantly affects actin organization in the MTs. These results demonstrate the crucial role of caspase-3/Drice in maintaining actin homeostasis and tubule morphogenesis. This study highlights the importance of caspase activity beyond apoptosis and its potential function in the developmental and physiological processes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/679759v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@162c4b2org.highwire.dtl.DTLVardef@15fabdcorg.highwire.dtl.DTLVardef@c0ec3org.highwire.dtl.DTLVardef@19d2f83_HPS_FORMAT_FIGEXP M_FIG C_FIG