1) is an important regulator of UPR signaling in
B. cinerea. Bag1 negatively regulates the central
UPR components Ire1, Hac1, and Bip1, suggesting a protective and important function in promoting ER homeostasis. Absence of Bag1
results in increased sensitivity towards cell
wall or ER stress-inducing compounds, and
functionality of Bag1 is furthermore important
for normal vegetative growth, formation of conidia, sclerotia, and full virulence in tomato
infection assays (Zhang et al. 2019).
3. Magnaporthe oryzae (Pyricularia oryzae)
The filamentous ascomycete Magnaporthe oryzae is the causal agent of rice blast. M. oryzae
exhibits a hemibiotrophic life cycle, starting
with an initial biotrophic phase, in which
plant penetration and initial colonization
occurs that is followed by the necrotrophic
stage featuring massive proliferation and host
colonization culminating in the formation of
conidia for further dissemination (Dean et al.
2012; Yan and Talbot 2016; Zhang et al. 2016a).
The function of the UPR in virulence of M.
oryzae has been investigated with respect to
the individual contributions of the S. cerevisiae
homologs of Hac1, Lhs1, Err1 (ER retention
receptor 1), and the MAPK Mps1. Deletion
mutants of individual genes encoding these
proteins show strongly reduced virulence, illustrating the central role of UPR in virulence of
M. oryzae. Besides Kar2/Bip1, Lhs1 represents
the major ER chaperone, being crucial for ER
protein folding and ER protein homeostasis.
Absence of Lhs1 results in increased UPR activity and reduced vegetative growth and conidiation. Defects in protein translocation across the
ER membrane support a function of Lhs1 for
efficient protein secretion, including effector
proteins such as AVR-Pita. During pathogenic
development Dlhs1 mutants are defective in
plant penetration and biotrophic invasion of
susceptible host plants. Interestingly, all defects
of the Dlhs1 mutant are rescued by overexpression of Sil1, which functions as a nucleotide
exchange factor for Kar2/Bip1 in S. cerevisiae
(Steel et al. 2004). In genome-wide studies
focusing on the role of bZIP transcription factors in M. oryzae, the homolog of Hac1 was
identified (Kong et al. 2015; Tang et al. 2015).
MoHac1 mutants display strongly reduced virulence in leaf infection assays, which is
connected to reduced vegetative growth, ER
stress resistance, and the almost complete
absence of conidiation. Expression of Mohac1
is reported to be significantly reduced during
invasive growth (72 hours post inoculation) in
rice or barley leaves (Mathioni et al. 2011),
suggesting that basal UPR activity is crucial
for disease development. ER-resident proteins
depend on their constant reimport into the ER
after accidental transition into the Golgi, for
proper subcellular localization and accumulation in the ER (Hardwick et al. 1990). Cterminal ER retention motifs (HDEL/KDEL
and derivatives thereof) are bound by
membrane-localized receptors preventing the
transit of HDEL/KDEL-containing proteins
through the secretory pathway. Mutants of the
M. oryzae HDEL receptor Err1 show severe
defects in vegetative growth and formation of
aberrant conidia, which fail to adhere to the
plant surface but produce functional appressoria and cause disease (Goh et al. 2017). The
cell wall integrity (CWI) MAPK Mps1 is
required for full UPR activity and thus represents a modulatory factor of the UPR in M.
oryzae. CWI and UPR pathways show crossregulation since phosphorylation of Mps1 is
increased in response to cell wall stress and by
endogenous and exogenous ER stress (Yin
et al. 2016).
4. Ustilago maydis
Ustilago maydis is a facultatively biotrophic
basidiomycete and the causal agent of corn
smut disease, inducing tumor (gall) formation
of its host plant maize (Zea mays) (Brefort et al.
2009). The analysis of UPR signaling in U. maydis revealed distinct adaptations of the ER
stress response to the biotrophic lifestyle and
fungal/plant interaction. U. maydis displays a
dimorphic life cycle in which the pathogenic
stage is induced after mating of saprotrophically growing and noninfectious haploid sporidia, to form the infectious biotrophic filament.
The heterodikaryotic filament elongates by tip
growth, as the cell cycle is arrested in the G2
60
R. Harting and K. Heimel
B. cinerea. Bag1 negatively regulates the central
UPR components Ire1, Hac1, and Bip1, suggesting a protective and important function in promoting ER homeostasis. Absence of Bag1
results in increased sensitivity towards cell
wall or ER stress-inducing compounds, and
functionality of Bag1 is furthermore important
for normal vegetative growth, formation of conidia, sclerotia, and full virulence in tomato
infection assays (Zhang et al. 2019).
3. Magnaporthe oryzae (Pyricularia oryzae)
The filamentous ascomycete Magnaporthe oryzae is the causal agent of rice blast. M. oryzae
exhibits a hemibiotrophic life cycle, starting
with an initial biotrophic phase, in which
plant penetration and initial colonization
occurs that is followed by the necrotrophic
stage featuring massive proliferation and host
colonization culminating in the formation of
conidia for further dissemination (Dean et al.
2012; Yan and Talbot 2016; Zhang et al. 2016a).
The function of the UPR in virulence of M.
oryzae has been investigated with respect to
the individual contributions of the S. cerevisiae
homologs of Hac1, Lhs1, Err1 (ER retention
receptor 1), and the MAPK Mps1. Deletion
mutants of individual genes encoding these
proteins show strongly reduced virulence, illustrating the central role of UPR in virulence of
M. oryzae. Besides Kar2/Bip1, Lhs1 represents
the major ER chaperone, being crucial for ER
protein folding and ER protein homeostasis.
Absence of Lhs1 results in increased UPR activity and reduced vegetative growth and conidiation. Defects in protein translocation across the
ER membrane support a function of Lhs1 for
efficient protein secretion, including effector
proteins such as AVR-Pita. During pathogenic
development Dlhs1 mutants are defective in
plant penetration and biotrophic invasion of
susceptible host plants. Interestingly, all defects
of the Dlhs1 mutant are rescued by overexpression of Sil1, which functions as a nucleotide
exchange factor for Kar2/Bip1 in S. cerevisiae
(Steel et al. 2004). In genome-wide studies
focusing on the role of bZIP transcription factors in M. oryzae, the homolog of Hac1 was
identified (Kong et al. 2015; Tang et al. 2015).
MoHac1 mutants display strongly reduced virulence in leaf infection assays, which is
connected to reduced vegetative growth, ER
stress resistance, and the almost complete
absence of conidiation. Expression of Mohac1
is reported to be significantly reduced during
invasive growth (72 hours post inoculation) in
rice or barley leaves (Mathioni et al. 2011),
suggesting that basal UPR activity is crucial
for disease development. ER-resident proteins
depend on their constant reimport into the ER
after accidental transition into the Golgi, for
proper subcellular localization and accumulation in the ER (Hardwick et al. 1990). Cterminal ER retention motifs (HDEL/KDEL
and derivatives thereof) are bound by
membrane-localized receptors preventing the
transit of HDEL/KDEL-containing proteins
through the secretory pathway. Mutants of the
M. oryzae HDEL receptor Err1 show severe
defects in vegetative growth and formation of
aberrant conidia, which fail to adhere to the
plant surface but produce functional appressoria and cause disease (Goh et al. 2017). The
cell wall integrity (CWI) MAPK Mps1 is
required for full UPR activity and thus represents a modulatory factor of the UPR in M.
oryzae. CWI and UPR pathways show crossregulation since phosphorylation of Mps1 is
increased in response to cell wall stress and by
endogenous and exogenous ER stress (Yin
et al. 2016).
4. Ustilago maydis
Ustilago maydis is a facultatively biotrophic
basidiomycete and the causal agent of corn
smut disease, inducing tumor (gall) formation
of its host plant maize (Zea mays) (Brefort et al.
2009). The analysis of UPR signaling in U. maydis revealed distinct adaptations of the ER
stress response to the biotrophic lifestyle and
fungal/plant interaction. U. maydis displays a
dimorphic life cycle in which the pathogenic
stage is induced after mating of saprotrophically growing and noninfectious haploid sporidia, to form the infectious biotrophic filament.
The heterodikaryotic filament elongates by tip
growth, as the cell cycle is arrested in the G2
60
R. Harting and K. Heimel