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Noncanonical Functions of BCL-2 Proteins in the Nervous System

  • Chapter
BCL-2 Protein Family

Part of the book series: Advances in Experimental Medicine and Biology ((volume 687))

Abstract

BCL-2 family proteins form heterodimers or homo-oligomers to inhibit or induce apoptotic cell death, respectively. They often relocalize from the cytoplasm to mitochondria to carry out these functions. The traditional model is that in healthy cells, anti-death family members hold pro-death BCL-2 family members in check. Upon receiving a death stimulus, another set of proteins (BH3-only proteins) inactivate the protective BCL-2 proteins, forcing them to release their pro-death partners that are subsequently triggered to oligomerize and porate the mitochondrial outer membrane leading to cell death. In support of this traditional view, there is a preponderance of supporting evidence derived from the study of events that occur following treatment of cells with a death stimulus. Knockout and mutant mice also exhibit many developmental and treatment-induced phenotypes consistent with this model of antagonism between BCL-2 family proteins. Emphasis is logically placed on those phenotypes that support the model. However, this working model of BCL-2 family interactions has become so engrained that alternative, potentially valid interpretations are sometimes dismissed. Therefore, it is useful to consider the evidence that seems contrary to accepted models. In particular, the analysis of BCL-2 family functions in the nervous system has revealed unexpected outcomes that can serve to further stimulate critical probing of the yet unknown biochemical functions of BCL-2 proteins.

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Author information

Authors and Affiliations

  1. Department of Molec Microb and Immunol, Johns Hopkins (JHSPH), 615 N Wolfe St., Baltimore, Maryland, 21205, USA

    J. Marie Hardwick

  2. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

    Heather M. Lamb

  3. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

    Heather M. Lamb

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  1. Heather M. Lamb
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  2. J. Marie Hardwick
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Correspondence to J. Marie Hardwick .

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Editors and Affiliations

  1. Institute of Biomedical Sciences, FONDAP Center for Molecular Studies of the Cell (CEMC) Millennium Nucleus for Neural Morphogenesis (NEMO), University of Chile, Santiago, Chile

    Claudio Hetz PhD

  2. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA

    Claudio Hetz PhD

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Lamb, H.M., Hardwick, J.M. (2010). Noncanonical Functions of BCL-2 Proteins in the Nervous System. In: Hetz, C. (eds) BCL-2 Protein Family. Advances in Experimental Medicine and Biology, vol 687. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6706-0_7

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