Growth, Differentiation and Sexuality

Clb2p and Cdc28p complex which phosphorylates
the Nim-1-related kinase Gin4p and the PAK Cla4p
(Longtine et al. 2000). Gin4p and Cla4p are required
for the formation of the septin ring (Longtine et al.
2000; Mortensen et al. 2002; Fig. 1.5).
4. Pseudohyphal Growth
Under conditions of nitrogen starvation, diploid S.
cerevisiae cells undergo a dimorphic transition involving
changes in cell shape and division, termed
pseudohyphal growth (Fig. 1.2A). Unlike the ellipsoidal
cells, pseudohyphal cells are elongate and
do not separate completely. The initiation of pseudohyphal
growth requires polarity reestablishment
and changes to actin polymerisation at the terminal
ends of pseudohyphal cells. Although the mechanisms
of polarised growth establishment during
pseudohyphal growth is not as well characterised
as budding, it is clear that this process uses some
of the same proteins and mechanism (Table 1.1).
However, unlike budding which operates on intrinsic
cues, pseudohyphal growth is regulated by
signal transduction pathways which relay extrinsicsignalsandleadtotheup-regulationofgenes
required for changes to the cell’s shape, adhesion
properties and budding pattern.
The signal(s) inducing pseudohyphal growth
remains unclear, but two signalling pathways have
been implicated in pseudohyphal growth, a cAMP
signalling pathway and a MAPK signalling pathway.
The cAMP pathway signals through a heterotrimeric
G protein (Gpa2p) which is associated
with the Gpr1p glucose-sensing G protein coupled
receptor (Lengeler et al. 2000). This signal and/or
a signal from GTP-bound active Ras2p leads to activation
of adenylate cyclase and results in the production
of cAMP (Lengeler et al. 2000). The second
pathway regulating pseudohyphal growth is
also mediated by the Ras2p GTPase. GTP-bound
Ras2p activates the GEF Cdc24p, which catalyses
the GDP to GTP exchange of Cdc42p. Cdc42p-GTP
consequently interacts with, and phosphorylates
the PAK Ste20p, which results in the sequential
phosphorylation and activation of components of
the mitogen-activated protein kinase (MAPK) cascade
(Madhani and Fink 1997).
Similarly to S. cerevisiae, there are two signalling
pathways in C. albicans which regulate the
transition from budding yeast to a filamentous
form in response to environmental stimuli (such
as pH, temperature and serum) – a cAMP-PKA
pathwayandaMAPKpathway,bothofwhichare
Generating Fungal Cell Types 11
activated by the C. albicans RAS1/2 homologue,
RAS1 (Lo et al. 1997; Lengeler et al. 2000). Ras1p
regulates the activity of adenylate cyclase, which
in turn regulates the cAMP pathway, and which
is also regulated by a G-protein α subunit (Toda
et al. 1985). Ras1p is considered to control Cdc42p
activity, which leads to activation of the MAPK cascade
(Leberer et al. 1996, 2001). Similarly to S. cerevisiae
and C. albicans,acAMPandaRassignalling
pathwayalsoleadtotheactivationofaMAPKcascade
regulating yeast-hyphal morphogenesis in the
plant pathogen Ustilago maydis (Lee and Kronstad
2002; see Chap. 18, this volume).
In addition to the conservation of signalling
pathways regulating morphogenesis, C. albicans requires
some of the same factors for the establishment
of polarisation during filamentous growth as
does S. cerevisiae. SimilarlytoS. cerevisiae, the
guanine exchange factor Cdc24p, the Rho GTPase
Cdc42p and, to a lesser extent, the Ras-like GTPase
Rsr1p are required for the establishment of polarisation
during filamentous growth in C. albicans
(Yaar et al. 1997; Ushinsky et al. 2002; Bassilana
et al. 2003; Table 1.1). Polarity is also thought to
be established by phosphorylation of myosins by
PAKs activated by Cdc42p, as mutations in both
the PAKs, Ste20p and Cla4p, and myosin-encoding
Myo5p (a homologue of S. cerevisiae Myo3/5p) resultinalossoffilamentousgrowthandincorrect
localisation of cortical actin at cell tips (Oberholzer
et al. 2002; Table 1.1). The Cdc24p, Cdc42p and
Rsr1p proteins are also required for the initiation
of polarised hyphal growth in the simple mycelial
fungus A. gossypii (Wendland and Philippsen 2001;
Bauer et al. 2004).
5. The Establishment of Polarised Growth
in Mycelial Fungi – Conidial Germination
The formation of dormant spores is common in
fungi, and these spores can be either sexually or
asexually derived. Under appropriate conditions,
Fig. 1.6. Conidial germination. The dormant conidium begins
germination after activation by environmental signals,
and begins isotropic expansion (swelling). After mitosis,
a site of polarisation is established and the conidium extends
a germ tube. As the growth tip extends, nuclear division
continues and septation is triggered to partition cells