Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 13:11:601405.
doi: 10.3389/fimmu.2020.601405. eCollection 2020.

To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins

Patrycja A Krawczyk  1 , Marco Laub  1 , Patrycja Kozik  1
Affiliations
Review

To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins

Patrycja A Krawczyk et al. Front Immunol. .

Abstract

Pore-forming proteins (PFPs) are present in all domains of life, and play an important role in host-pathogen warfare and in the elimination of cancers. They can be employed to deliver specific effectors across membranes, to disrupt membrane integrity interfering with cell homeostasis, and to lyse membranes either destroying intracellular organelles or entire cells. Considering the destructive potential of PFPs, it is perhaps not surprising that mechanisms controlling their activity are remarkably complex, especially in multicellular organisms. Mammalian PFPs discovered to date include the complement membrane attack complex (MAC), perforins, as well as gasdermins. While the primary function of perforin-1 and gasdermins is to eliminate infected or cancerous host cells, perforin-2 and MAC can target pathogens directly. Yet, all mammalian PFPs are in principle capable of generating pores in membranes of healthy host cells which-if uncontrolled-could have dire, and potentially lethal consequences. In this review, we will highlight the strategies employed to protect the host from destruction by endogenous PFPs, while enabling timely and efficient elimination of target cells.

Keywords: gasdermins; immunity; membrane attack complex; membrane integrity; perforins; pore-forming proteins.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A diagram illustrating the domain structures and selected regulatory features of mammalian PFPs.
Figure 2
Figure 2
A schematic summary of the mechanisms involved in regulation and activation of perforin-1, perforin-2, MAC, and gasdermins. (A) Cell types or tissues in which the PFP is constitutively expressed (inducible expression is highlighted with ↑). (B) Processing and trafficking steps involved in synthesis of the “stored” form of the PFP. The last row corresponds to the storage compartment. (C) Immune system components which initiate pore formation, and ligands they recognize. (D) A schematic representation of the events that precede pore assembly. (E) Targeted membranes.
See this image and copyright information in PMC

References

    1. Peraro MD, van der Goot FG. Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol (2016) 14(2):77–92. 10.1038/nrmicro.2015.3 - DOI - PubMed
    1. Anderluh G, Kisovec M, Kraševec N, Gilbert RJC. Distribution of MACPF/CDC Proteins. In: Anderluh G, Gilbert R, editors. MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Dordrecht: Springer Netherlands; (2014). 10.1007/978-94-017-8881-6_2 - DOI
    1. Liu X, Lieberman J. Knocking ‘em dead: pore-forming proteins in immune defense. Annu Rev Immunol (2020) 38(1):455–85. 10.1146/annurev-immunol-111319-023800 - DOI - PMC - PubMed
    1. Nuttall G. Experimente über die bacterienfeindlichen Einflüsse des thierischen Körpers. Z Hyg Infektionskr (1888) 4(1):353–94. 10.1007/BF02188097 - DOI
    1. Buchner HEA. Über die bakterientötende Wirkung des Zellfreien Blutserums. I and II. Zentralbl Bakteriol (1889) 5:817–23.

Publication types

Substances