Growth, Differentiation and Sexuality

Fig. 18.2. Basic outline of the MAP kinase module transmitting
the pheromone signal. Components of the MAP
kinase module (hexagons)-regulate pheromone response,
functional infectious hyphae, conjugation hyphae as well
as infection structures. Upstream components are shown
as ovals (Ras association domain and sterile alpha motive
are symbolized by encircled R and S respectively). The
pheromone-responsive MAPK module regulates Prf1 (circle)
which, in turn, induces a and b gene expression, as well
as expression of the prf1 gene (rectangle). Possible autoregulation
of prf1 is indicated by the presence of pheromone
response elements (triangles) upstream of the transcriptional
start site (wavy line)
model fungi such as Saccharomyces cerevisiae
and Schizosaccharomyces pombe,anevolutionarily
conserved pheromone-responsive mitogen-activated
protein kinase module (MAPK) has been
identified which transduces the pheromone signal
towards Prf1 (Kaffarnik et al. 2003; Müller et al.
2003b; Fig. 18.2). This module consists of the MAP
kinase Kpp2/Ubc3, the MAPK kinase Fuz7/Ubc5,
and the MAPKK kinase Kpp4/Ubc4 (Banuett and
Herskowitz 1994; Mayorga and Gold 1999; Müller
et al. 1999, 2003b; Andrews et al. 2000; Fig. 18.2). In
addition to direct activation of Prf1 by phosphorylation
via Kpp2, the pheromone-activated MAPK
module triggers transcriptional activation of the
prf1 promoter as well as formation of conjugation
hyphae (Kaffarnik et al. 2003; Müller et al. 2003b).
Conjugationhyphaearethefirstmorphological
Regulatory and Structural Networks in Ustilago maydis 377
response to be seen after pheromone stimulation.
They usually develop at one pole of the cell, grow
towards the pheromone source, and fuse at their
tips (Snetselaar et al. 1996). The formation of
conjugation hyphae is independent of Prf1 function,
indicating that this morphological program
is controlled by a different transcription factor
ormaybetriggeredthroughdirectmodification
of components of the cytoskeleton (Müller et al.
2003b; Fig. 18.2).
At present it is not known how the signal from
the pheromone-bound activated receptor is transduced
to the MAPKKK Kpp4/Ubc4. A factor likely
to be involved in this signalling step is the putative
adapter protein Ubc2 (Fig. 18.2), which shares similarity
with the pheromone signalling component
Ste50p from S. cerevisiae. Ubc2 contains several
protein interaction domains such as a sterile alpha
motif (SAM), a Ras association domain (RA),
and a Src homology domain (SH3). Since ubc2Δ
strains are impaired in pheromone response and
virulence, it has been suggested that Ubc2 funnels
signalling information to the MAPK module (Mayorga
and Gold 2001; Fig. 18.2). The interaction between
Ubc2 and MAPKKK Kpp4/Ubc4 which could
be mediated by the SAM domain of Kpp4/Ubc4 has
been described for the Ste50p/Ste11p interaction in
S. cerevisiae (Müller et al. 2003b; Grimshaw et al.
2004; Fig. 18.2). Further components potentially involved
in pheromone signalling are the small G protein
Ras2 and the guanine nucleotide exchange factor
(GEF) Sql2. Ras2 is epistatic to components of
the pheromone-responsive MAPK module, and expression
of a constitutively active version Ras2 G16V
elicits increased mfa1 expression. Thus, Ras2 could
feed into MAPK signalling via the Ras association
(RA) domains of Ubc2 or Kpp4/Ubc4 (Lee and Kronstad
2002; Müller et al. 2003a; Fig. 18.2). Genetic
evidence indicates that the GEF Sql2 might function
as cognate activator of Ras2 (Müller et al. 2003a;
Fig. 18.2).
Research during the last decade has revealed
that the pheromone signalling pathway in U.
maydis is not a simple linear pathway consisting of
insulated signalling components which function
only during pheromone response. On the contrary,
intensive crosstalk with other signalling pathways
exists and is essential to orchestrate mating and
subsequent pathogenic development (Feldbrügge
et al. 2004; see below). A connection between
pheromone signalling and nutritional and cell
cycle signalling is well established in S. pombe
and S. cerevisiae (Davey 1998; Elion 2000). For U.