Abstract
Spermatozoa are generated and mature within a germline syncytium. Differentiation of haploid syncytial spermatids into single motile sperm requires the encapsulation of each spermatid by an independent plasma membrane and the elimination of most sperm cytoplasm, a process known as individualization. Apoptosis is mediated by caspase family proteases. Many apoptotic cell deaths in Drosophila utilize the REAPER/HID/GRIM family proapoptotic proteins. These proteins promote cell death, at least in part, by disrupting interactions between the caspase inhibitor DIAP1 and the apical caspase DRONC, which is continually activated in many viable cells through interactions with ARK, the Drosophila homolog of the mammalian death-activating adaptor APAF-1. This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC. Here we demonstrate that ARK- and HID-dependent activation of DRONC occurs at sites of spermatid individualization and that all three proteins are required for this process. dFADD, the Drosophila homolog of mammalian FADD, an adaptor that mediates recruitment of apical caspases to ligand-bound death receptors, and its target caspase DREDD are also required. A third apoptotic caspase, DRICE, is activated throughout the length of individualizing spermatids in a process that requires the product of the driceless locus, which also participates in individualization. Our results demonstrate that multiple caspases and caspase regulators, likely acting at distinct points in time and space, are required for spermatid individualization, a nonapoptotic process.
Highlights
Most, if not all, cells have the potential to carry out the apoptotic cell death program (Jacobson et al 1997)
Our observations demonstrate that multiple caspases and caspase regulators, acting at distinct points in space and time, are utilized to promote spermatid individualization
In one pathway, whose mechanism of activation is unknown, active DRICE appears throughout elongated spermatids just as individualization begins
Summary
If not all, cells have the potential to carry out the apoptotic cell death program (Jacobson et al 1997). In Drosophila the apoptotic effector caspase DRICE is cleaved and activated throughout the length of elongated spermatids, and testis-specific expression of the baculovirus caspase inhibitor p35 results in male sterility, despite the fact that apoptosis is not an obligate step in spermatogenesis (Arama et al 2003). These observations demonstrate that caspase activity is important for male fertility, but leave a number of questions unanswered: For what events in spermatid differentiation are caspases required? These observations demonstrate that caspase activity is important for male fertility, but leave a number of questions unanswered: For what events in spermatid differentiation are caspases required? Which caspases mediate this requirement? How are they activated and where do they act? And how do these cells avoid apoptosis?
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