Growth, Differentiation and Sexuality

380 M. Feldbrügge et al.
et al. 2004; Fig. 18.4). Transcription of crk1 is
regulated antagonistically by PKA and MAPK
signalling, and overexpression of crk1 is sufficient
to trigger filament formation (Garrido and Pérez-
Martín 2003; Fig. 18.4). Potential transcriptional
regulators for crk1 couldbeHgl1andSql1.Hgl1,
a PKA target in vitro, was identified as suppressor
for the filamentous phenotype of adr1Δ mutants
(Dürrenberger et al. 2001). Sql1, a functional
homologue of the transcriptional repressor Ssn6p
from S. cerevisiae, hasbeenshowntosuppress
the phenotype of an activated cAMP pathway
(Loubradou et al. 2001; Fig. 18.4).
The induction of filaments by Crk1 is also
regulated posttranscriptionally by Fuz7/Ubc5- and
Kpp2/Ubc3-dependent phosphorylation of the
N- and C-terminal domains of Crk1 respectively.
Interestingly, the MAPK sites in the C terminus
are dispensable for Crk1 function during mating
(Garrido et al. 2004; Figs. 18.3 and 18.4). This
results in a complex mode of regulation in which
the N-terminal part of Crk1, which has MAPK
activity, is a MAPKK target whereas the C terminus
is a MAPK target (Fig. 18.4).
Although extensive progress has been made
in identifying components of the PKA/MAPK signalling
network, the signals perceived via these
pathways, besides pheromones, are waiting to be
uncovered. Promising candidates for such signals
are specific lipids and the pH of the environment,
which were shown to stimulate this signalling network
during filament formation (Klose et al. 2004;
Martinez-Espinoza et al. 2004; see below).
C. Signalling Network During
Pathogenic Development
In addition to their role in regulating mating and
morphogenesis, PKA and MAPK signalling are important
determinants of pathogenic development.
With the exception of the G protein β subunit
Bpp1, all components of cAMP signalling identified
to date are essential for pathogenicity (Garcia-
Pedrajas et al. 2004; Müller et al. 2004). Mutants
with different levels of perturbation of cAMP signalling
arrest at specific points of the pathogenicity
program. Filamentously growing mutant strains affectedinthecAMPpathway,suchasgpa3Δ,
uac1Δ
and adr1Δ, do not cause any disease symptoms
(Gold et al. 1994; Regenfelder et al. 1997; Dürrenberger
et al. 1998). Thus, the induction of filamentous
growth through low PKA activity is not suffi-
cient to trigger pathogenic development, stressing
the need for an active bE/bW heterodimer during
this process (see below).
Mutants such as ubc1 R312Q , gpa3 Q206L or hgl1Δ
which reflect increased PKA activity elicit the
formation of tumours devoid of black teliospores
(Krüger et al. 2000; Dürrenberger et al. 2001).
Interestingly, gpa3 Q206L -expressing strains form
abnormal tumours with shoot-like structures
(Krüger et al. 2000). These results indicate that
fungal development during growth in planta
requires tightly regulated levels of PKA activity,
and inadequate levels of PKA activity affect
communication with the host during tumour
differentiation.
Given the fact that MAPK signalling is a central
regulator for mating and morphogenesis, it
was no surprise that mutants affected in MAPK
signalling are affected also in pathogenicity.
kpp4Δ and fuz7Δ strains are non-pathogenic
(Banuett and Herskowitz 1994; Müller et al.
2003b), whereas kpp2Δ mutants are reduced in
virulence (Müller et al. 1999). This apparent
discrepancy was resolved when a third MAP
kinase, kpp6, was identified as bE/bW-regulated
MAPK with partially overlapping functions to
kpp2 (Fig. 18.2). kpp2Δ/kpp6Δ double mutants
are non-pathogenic, supporting the notion that
these two MAPKs exert important but redundant
functions during pathogenic development
(Brachmann et al. 2003). By expressing mutant
versions of kpp2 and kpp6 which can no longer
be activated by their corresponding MAPKK, it
was furthermore demonstrated that Kpp2 is required
for appressorium formation whereas Kpp6
functions at a later stage during plant penetration
(Brachmann et al. 2003). Given the finding that
pheromones and receptors are dispensable for
pathogenic development after cell fusion, the MAP
kinase module, which transmits the pheromone
signal, must be activated by different input signals
during pathogenesis. It was recently shown that
U. maydis cells respond to the presence of fatty
acids or triglycerides by switching to filamentous
growth. Since mutations in ras2, fuz7 and ubc3
block this reaction (Klose et al. 2004), the MAP
kinase module transmitting the pheromone signal
must be required for this response. In addition, low
pH signalling was also demonstrated to involve
this module (Martinez-Espinoza et al. 2004). It will
be a future challenge to determine whether these
signals are indeed used in communication with
the plant.