refinement of this defense strategy, the plant
immune system includes decoys representing
mimics of effector targets that serve solely to
detect pathogen intrusion. Although in many
cases the mechanistic details of NLR function
are still unknown (in particular in the case of
plant NLRs), the general working paradigm
for these receptors corresponds to a ligandinduced oligomerization model. The receptors
are thought to recognize PAMPs or DAMPs
(damage-associated molecular patterns) via
the C-terminal LRR domain. Ligand binding
then leads to receptor oligomerization
mediated by the central nucleotide-binding
domain. The oligomerization step into
discrete-sized or open-ended oligomers then
leads to activation of the N-terminal effector
or signaling domain. This general scheme probably shows many variations and exceptions, for
instance, elicitor binding was shown to involve
the NOD domain rather than the C-terminal
LRR domain in certain mouse NLRs (Tenthorey
et al. 2014). The effector or signaling domains
occurring at the N-terminus of NLRs differ in
plant and animal lineages. Two main types are
found in plants, the CC (for coiled coil) and TIR
domains, while in animal lineages one finds
predominantly death-fold domains (such as
CARD, PYD, and DD), which engage into
higher-order homotypic interactions (Jones
et al. 2016; Vajjhala et al. 2017).
While this family of proteins is intensively
studied in plant and animal lineages, less is
known about fungal NLR homologs. A significant fraction of the work devoted to the characterization of NLR in fungi was developed in
connection with the mechanistic dissection of a
self/non-self recognition process known as heterokaryon incompatibility (Chevanne et al.
2009, 2010; Choi et al. 2012; Daskalov et al.
2015b; Heller et al. 2018; Paoletti et al. 2007;
Saupe et al. 1995a; Zhang et al. 2014). Incompatibility occurs both in ascomycetes and basidiomycetes fungi when strains of unlike
genotype undergo anastomosis (somatic cell
fusion). The phenomenon was first described
in the plant pathogen Diaporthe perniciosa in
1923 by Dorothy M. Cayley (a British mycologist coworker of W. Bateson in the “ladies lab”
at the John Innes Center) and termed “mutual
aversion” (Cayley 1923). Incompatibility is
genetically controlled by so-called heterokaryon incompatibility loci (Aanen et al. 2010;
Daskalov et al. 2017; Paoletti 2016; Saupe 2000).
Incompatibility systems can either be allelic
(incompatible alleles of the same locus) or
non-allelic (incompatibility is caused by gene
interactions at unlinked loci) (Pinan-Lucarre
et al. 2007). Karl Esser, the historical editor of
this compendium, was a pioneer in the biochemical and genetic dissection of incompatibility in Podospora (Esser 1965). Over the years
it has become clear that in several species,
incompatibility genes encode proteins displaying an NLR-like domain architecture. Although
direct functional evidence for an immune function of NLRs in fungi is currently still lacking, a
role for this class of proteins in non-self recognition processes and the control of programmed cell death is established in different
species (Choi et al. 2012; Daskalov et al. 2015b;
Heller et al. 2018; Saupe et al. 1995a). Further
indirect evidence supports the hypothesis that
fungal NLR-type proteins could play a similar
role as in animals and plants (Paoletti and
Saupe 2009; Uehling et al. 2017), raising the
question of the evolutionary scenario explaining the possible common use for host defense of
this type of receptor in these three lineages.
The aim of this brief chapter is to review the
role of NLRs in fungal incompatibility and to
propose a general description of NLR repertoires in fungal genomes. Similarities and differences of this protein family in fungal as
compared to plant and animal lineages will be
discussed. We will also review a specific mechanism of NLR-mediated signal transduction
common in fungi and involving prion propagation of an amyloid fold. We discuss the importance of taking into account the proposed
immune role of fungal NLRs to interpret
the evolutionary trajectory of this protein
architecture in plants, animals, and fungi
(and bacteria).
II. NLRs in Fungal Incompatibility
Heterokaryon incompatibility manifests itself
as a programmed cell death reaction occurring
rapidly after cell fusion between genetically
124
A. Daskalov et al.
immune system includes decoys representing
mimics of effector targets that serve solely to
detect pathogen intrusion. Although in many
cases the mechanistic details of NLR function
are still unknown (in particular in the case of
plant NLRs), the general working paradigm
for these receptors corresponds to a ligandinduced oligomerization model. The receptors
are thought to recognize PAMPs or DAMPs
(damage-associated molecular patterns) via
the C-terminal LRR domain. Ligand binding
then leads to receptor oligomerization
mediated by the central nucleotide-binding
domain. The oligomerization step into
discrete-sized or open-ended oligomers then
leads to activation of the N-terminal effector
or signaling domain. This general scheme probably shows many variations and exceptions, for
instance, elicitor binding was shown to involve
the NOD domain rather than the C-terminal
LRR domain in certain mouse NLRs (Tenthorey
et al. 2014). The effector or signaling domains
occurring at the N-terminus of NLRs differ in
plant and animal lineages. Two main types are
found in plants, the CC (for coiled coil) and TIR
domains, while in animal lineages one finds
predominantly death-fold domains (such as
CARD, PYD, and DD), which engage into
higher-order homotypic interactions (Jones
et al. 2016; Vajjhala et al. 2017).
While this family of proteins is intensively
studied in plant and animal lineages, less is
known about fungal NLR homologs. A significant fraction of the work devoted to the characterization of NLR in fungi was developed in
connection with the mechanistic dissection of a
self/non-self recognition process known as heterokaryon incompatibility (Chevanne et al.
2009, 2010; Choi et al. 2012; Daskalov et al.
2015b; Heller et al. 2018; Paoletti et al. 2007;
Saupe et al. 1995a; Zhang et al. 2014). Incompatibility occurs both in ascomycetes and basidiomycetes fungi when strains of unlike
genotype undergo anastomosis (somatic cell
fusion). The phenomenon was first described
in the plant pathogen Diaporthe perniciosa in
1923 by Dorothy M. Cayley (a British mycologist coworker of W. Bateson in the “ladies lab”
at the John Innes Center) and termed “mutual
aversion” (Cayley 1923). Incompatibility is
genetically controlled by so-called heterokaryon incompatibility loci (Aanen et al. 2010;
Daskalov et al. 2017; Paoletti 2016; Saupe 2000).
Incompatibility systems can either be allelic
(incompatible alleles of the same locus) or
non-allelic (incompatibility is caused by gene
interactions at unlinked loci) (Pinan-Lucarre
et al. 2007). Karl Esser, the historical editor of
this compendium, was a pioneer in the biochemical and genetic dissection of incompatibility in Podospora (Esser 1965). Over the years
it has become clear that in several species,
incompatibility genes encode proteins displaying an NLR-like domain architecture. Although
direct functional evidence for an immune function of NLRs in fungi is currently still lacking, a
role for this class of proteins in non-self recognition processes and the control of programmed cell death is established in different
species (Choi et al. 2012; Daskalov et al. 2015b;
Heller et al. 2018; Saupe et al. 1995a). Further
indirect evidence supports the hypothesis that
fungal NLR-type proteins could play a similar
role as in animals and plants (Paoletti and
Saupe 2009; Uehling et al. 2017), raising the
question of the evolutionary scenario explaining the possible common use for host defense of
this type of receptor in these three lineages.
The aim of this brief chapter is to review the
role of NLRs in fungal incompatibility and to
propose a general description of NLR repertoires in fungal genomes. Similarities and differences of this protein family in fungal as
compared to plant and animal lineages will be
discussed. We will also review a specific mechanism of NLR-mediated signal transduction
common in fungi and involving prion propagation of an amyloid fold. We discuss the importance of taking into account the proposed
immune role of fungal NLRs to interpret
the evolutionary trajectory of this protein
architecture in plants, animals, and fungi
(and bacteria).
II. NLRs in Fungal Incompatibility
Heterokaryon incompatibility manifests itself
as a programmed cell death reaction occurring
rapidly after cell fusion between genetically
124
A. Daskalov et al.