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Can’t live without them, can live with them: roles of caspases during vital cellular processes

  • Apoptosis in Drosophila
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Abstract

Since the pioneering discovery that the genetic cell death program in C. elegans is executed by the cysteine-aspartate protease (caspase) CED3, caspase activation has become nearly synonymous with apoptosis. A critical mass of data accumulated in the past few years, have clearly established that apoptotic caspases can also participate in a variety of non-apoptotic processes. The roles of caspases during these processes and the regulatory mechanisms that prevent unrestrained caspase activity remain to be fully investigated, and may vary in different cellular contexts. Significantly, some of these processes, such as terminal differentiation of vertebrate lens fiber cells and red blood cells, as well as spermatid terminal differentiation and dendritic pruning of sensory neurons in Drosophila, all involve proteolytic degradation of major cellular compartments, and are conceptually, molecularly, biochemically, and morphologically reminiscent of apoptosis. Moreover, some of these model systems bear added values for the study of caspase activation/apoptosis. For example, the Drosophila sperm differentiation is the only system known in invertebrate which absolutely requires the mitochondrial pathway (i.e. Cyt c). The existence of testis-specific genes for many of the components in the electron transport chain, including Cyt c, facilitates the use of the Drosophila sperm system to investigate possible roles of these otherwise essential proteins in caspase activation. Caspases are also involved in a wide range of other vital processes of non-degenerative nature, indicating that these proteases play much more diverse roles than previously assumed. In this essay, we review genetic, cytological, and molecular studies conducted in Drosophila, vertebrate, and cultured cells, which underlie the foundations of this newly emerging field.

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Acknowledgments

We thank Ann H. Tang, Orly Reiner, Liat Ravid-Lustig, and Oren Schuldiner for critically reading the manuscript, and Ben-Zion Shilo for useful comments. We also would like to thank Steven Bassnett, Yasuki Ishizaki, Andreas Koenig, Martin Raff, and Darren Williams for the prompt permission to use their figures. Research in my laboratory is supported in part by the Morasha program of the Israel Science Foundation, Minerva foundation with funding from the Federal German Ministry for Education and Research, Israel Cancer Research Fund, German-Israeli Foundation for Scientific Research and Development, and the Moross Institute for Cancer Research. E.A. is an Alon Fellow with the Council for Higher Education of the Israeli Academy of Sciences and is also supported by grants from Lord Mitchell, The Henry S. & Anne S. Reich Research Fund for Mental Health, The Samuel M. Soref & Helene K. Soref Foundation, and The Chais Family Fellows Program for New Scientists. E.A. is the Incumbent of the Corinne S. Koshland Career Development Chair. Y.F-R. receives funding from the Israeli Ministry of Absorption in Science. We apologize to those whose work we did not cite because of either oversight on our part or space constraints.

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  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Yael Feinstein-Rotkopf & Eli Arama

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Feinstein-Rotkopf, Y., Arama, E. Can’t live without them, can live with them: roles of caspases during vital cellular processes. Apoptosis 14, 980–995 (2009). https://doi.org/10.1007/s10495-009-0346-6

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