The Evolutionary Origins of Programmed Cell Death Signaling

Hofmann, Kay

doi:10.1101/cshperspect.a036442

Cited by 36 publications

(29 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell death is an essential biological process for multicellular organisms including fungi, plants and animals [1], with important functions for development, tissue homeostasis and host defence. This article focuses on recent developments on cell death regulation and function in mice and humans with particular emphasis on the role of cell death in tissue homeostasis, inflammation and disease.…”

Section: Introductionmentioning

confidence: 99%

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

Schwarzer

Laurien

Pasparakis

2020

Current Opinion in Cell Biology

122

View full text Add to dashboard Cite

Necroptosis and pyroptosis are inflammatory forms of regulated necrotic cell death as opposed to apoptosis that is generally considered immunologically silent. Recent studies revealed unexpected links in the pathways regulating and executing cell death in response to activation of signalling cascades inducing apoptosis, necroptosis and pyroptosis. Emerging evidence suggests that RIPK1 and caspase-8 control the crosstalk between apoptosis, necroptosis and pyroptosis and determine the type of cell death induced in response to activation of cell death signalling.

show abstract

Section: Introductionmentioning

confidence: 99%

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

Schwarzer

Laurien

Pasparakis

2020

Current Opinion in Cell Biology

122

View full text Add to dashboard Cite

show abstract

“…The N-terminal HELL domain of HELLP shows homology to the 4HB domain of MLKL responsible for membrane permeation in mammalian necroptosis. HELLP induced programmed cell death thus appears to be related to a family of evolutionary widespread form of immune PCD which encompasses fungal cell death, necroptosis and cell death associated with the hypersensitive response in plants [22,34,35]. We propose that PNT1 and HELLP constitute a third amyloid immune-related signaling cascade controlling cell fate in P. anserina .…”

Section: Discussionmentioning

confidence: 99%

Partial prion cross-seeding between fungal and mammalian amyloid signaling motifs

Bardin

Daskalov

Barrouilhet

et al. 2020

Preprint

View full text Add to dashboard Cite

In fungi, NLR-based signalosomes activate downstream membrane-targeting cell-death inducing proteins by a mechanism of amyloid templating. In the species Podospora anserina, two such signalosomes, NWD2/HET-S and FNT1/HELLF have been described as well as an analogous system, involving a distinct amyloid signaling motif termed PP in the species Chaetomium globosum. The PP-motif bears resemblance to the RHIM and RHIM-like motifs controlling necroptosis in mammals and innate immunity in Drosophila. We identified here, a third NLR signalosome in Podospora anserina comprising a PP-motif and organized as a two-gene cluster encoding a NLR and a HELL-domain cell-death execution protein termed HELLP. We show that the PP-motif region of HELLP forms a prions we term [π] and that [π] prions trigger the cell-death inducing activity of full length HELLP. We detect no prion cross-seeding between HET-S, HELLF and HELLP amyloid motifs. In addition, we find that akin to PP-motifs, RHIM motifs from human RIP1 and RIP3 kinases are able to form prions in Podospora, and that [π] and [Rhim] prions cross-seed. Our study shows Podospora display three independent amyloid signalosomes. Based on the described functional similarity between RHIM and PP it appears likely that these amyloid motifs constitute evolutionary related cell-death signaling modules.Author summaryAmyloids are fibrillar protein polymers assembled from cross β-sheets. Pathogenic amyloids are responsible for a range of neuronal and systemic protein misfolding diseases. In addition, functional amyloids fulfill a variety of biological functions in microbes and animals. In fungi, amyloids control prion-like signaling pathways with roles in host defense and immune programmed cell death. These signaling pathways involve a Nod-like receptor and a cell-death execution protein activated through amyloid templating. In P. anserina two such amyloid signaling systems were identified so far. Here we identified and characterized a third amyloid signaling system comprising a different amyloid motif termed PP. We showed a total absence of cross-induction between the three P. anserina systems allowing for the co-existence of three independent amyloid signaling cascades in the same organism. An evolutionary relationship between fungal amyloid motifs and mammalian RHIM amyloid motif involved in the necroptosis pathway was previously suggested. We validated this assumption by showing that the human RHIM motif could not only propagate as a prion in P. anserina but also functionally cross-interact with the fungal PP-motif prions. These results point to a long term evolutionary conservation of amyloid signaling mechanisms from fungi to mammals.

show abstract

“…In a nutshell, in this incompatibility system, the [Het-s] prion acts as an activation switch of HET-S pore-forming activity. Remarka bly, the HeLo domain shows homology to other poreforming domains involved in regulated cell death, both in plants and animals, the four helix bundle domain of the mixed lineage kinase domain-like protein (MLKL) involved in necroptosis execution and coiled coil-related domains found in Nod-like receptors and other plant immune response proteins [11][12][13][14].…”

Section: [Het-s]/het-smentioning

confidence: 99%

The expanding scope of amyloid signalling

Daskalov

Saupe

2021

Prion

View full text Add to dashboard Cite

Formation of higher-order supramolecular complexes has emerged as a common principle underlying activity of a number of immune and regulated cell-death signalling pathways in animals, plants and fungi. Some of these signalosomes employ functional amyloid motifs in their assembly process. The description of such systems in fungi finds its origin in earlier studies on a fungal prion termed [Het-s], originally identified as a non-Mendelian cytoplasmic infectious element. Janine Beisson has been a key contributor to such early studies. Recent work on this and related systems offers a more integrated view framing this prion in a broader picture including related signalling systems described in animals. We propose here an auto-commentary centred on three recent studies on amyloid signalling in microbes. Collectively, these studies increase our understanding of fold conservation in functional amyloids and the structural basis of seeding, highlight the relation of fungal amyloid motifs to mammalian RHIM (RIP homotypic interaction motif) and expand the concept of Nod-like receptor-based amyloid signalosomes to the prokaryote reign.

show abstract

The Evolutionary Origins of Programmed Cell Death Signaling

Cited by 36 publications

References 79 publications

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

Partial prion cross-seeding between fungal and mammalian amyloid signaling motifs

The expanding scope of amyloid signalling

Contact Info

Product

Resources

About