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Multiple Apoptotic Caspase Cascades Are Required in Nonapoptotic Roles for Drosophila Spermatid Individualization

Huh, Jun R. and Vernooy, Stephanie Y. and Yu, Hong and Yan, Nieng and Shi, Yigong and Guo, Ming and Hay, Bruce A. (2004) Multiple Apoptotic Caspase Cascades Are Required in Nonapoptotic Roles for Drosophila Spermatid Individualization. PLoS Biology, 2 (1). pp. 43-53. ISSN 1544-9173. PMCID PMC300883. doi:10.1371/journal.pbio.0020015.

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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.

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Additional Information:© 2003 Huh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received September 28, 2003; Accepted November 14, 2003; Published December 15, 2003. Accession Numbers: The National Center for Biotechnology Information (NCBI) ( accession number for p35 is P08160. The FlyBase ( accession numbers of the sequences discussed in this paper are Ark (FBgn0024252), cyt-c-d (FBgn0000408), Dcp-1 (FBgn0010501), dFadd (FBgn0038928), Diap1 (FBgn0003691), Dredd (FBgn0020381), Drice (FBgn0019972), Dronc (FBgn0026404), Grim (FBgn0015946), Hid (FBgn0003997), and Reaper (FBgn0011706). We thank Jules Hoffmann, Bruno Lemaitre, Marco Di Fruscio, Kristen White, John Abrams, Alfonso Martinez-Arias, and Takashi Adachi-Yamada for fly stocks; M. E. Bre for AXO49; Lai Wang and Xiaodong Wang for anti-ARK antibodies; Pat Koen and Jean Edens for assistance with EM; and David Anderson for use of his confocal microscope. This work was supported by grants to BAH from the Ellison Medical Foundation and The Burroughs Wellcome Fund (New Investigators Award) and by National Institutes of Health grant R01 GM057422. Conflicts of interest: The authors have declared that no conflicts of interest exist. Author contributions: JRH and BAH conceived and designed the experiments. JRH and SYV performed the experiments. JRH and BAH analyzed the data. JRH, HY, NY, YS, MG, and BAH contributed reagents/materials/analysis tools. JRH and BAH wrote the paper.
Subject Keywords:b2tub, b2-tubulin; cyt-c-d, cytochrome c-d; DCP-1, Drosophila caspase-1; Dn, dominant negative; EM, electron microscopy; GMR, glass multimer reporter; IAP, inhibitor of apoptosis; IMD, immune deficiency; PGRP, peptidoglyclan recognition protein; RNAi, RNA interference
Issue or Number:1
PubMed Central ID:PMC300883
Record Number:CaltechAUTHORS:HUHpb04
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Official Citation:Huh JR, Vernooy SY, Yu H, Yan N, Shi Y, et al. (2004) Multiple Apoptotic Caspase Cascades Are Required in Nonapoptotic Roles for Drosophila Spermatid Individualization. PLoS Biol 2(1): e15
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:309
Deposited By: Archive Administrator
Deposited On:18 May 2005
Last Modified:08 Nov 2021 19:01

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