Growth, Differentiation and Sexuality

Calderone, Chap. 5, this volume, and The Mycota,
Vol. III, 2nd edn., Chap. 14). Since chitin is missing
in vertebrates and is essential for fungal cell wall integrity,
inhibition of the ability to synthesize chitin
is a promising target for antifungal drug therapies.
Polyoxins and nikkomycins are currently in use as
drugs that inhibit chitin synthesis (Ruiz-Herrera
and San-Blas 2003).
This section deals with the question of how
an orderly assembly of protein complexes at future
septal sites is accomplished, and which are
the major players identified so far. During evolution,
these protein complexes were apparently
highly conserved between fungi and animal cells,
which allows the identification of homologous proteins
in various organisms, either through genomic
sequencing projects or via PCR approaches using
degenerate primers based on conserved protein domains.
The Rho-GTPase Cdc42p complex plays an essentialroleincellpolarityestablishmentinfungi
(Johnson 1999; Wendland 2001). In S. cerevisiae,
Cdc42p is required to establish a new site of polarized
growth, resulting in bud emergence. This
position also defines the new bud neck (Fig. 6.3A).
Cdc42p initiates the assembly of both a septin and
an acto-myosin ring, described in the following
sections (Sanders and Field 1994; Gladfelter et al.
2001; Caviston et al. 2003).
A. The Septin Ring
In S. cerevisiae, the septin ring is composed of
a conserved family of mitotic septins encoded by
CDC3, CDC10, CDC11, CDC12, and SHS1, and
forms a cortical collar of septin filaments at the
mother-bud neck (Byers and Goetsch 1976). Due to
ahighdegreeofconservation,variousseptinshave
been isolated in other organisms, too (Neufeld and
Rubin 1994; Longtine et al. 1996; Field and Kellog
1999; Momany et al. 2001). Septins contain several
domains including an N-terminal region with
a potential phosphoinositide binding site, a core
region including a P-loop guanine nucleotide
binding motif, a septin-specific sequence, and
aC-terminaldomainthatinsomecasesincludes
a predicted coiled-coil region (Casamayor and
Snyder 2003). GTP/GDP binding and hydrolysis
have been demonstrated for septins, although
GTP turnover may be small in vivo (Field et al.
1996; Versele and Thorner 2004; Vrabioiu et al.
2004). Septins were first identified in S. cerevisiae
Septation in Fungi 111
Fig. 6.3. Assembly of protein complexes during septation/cytokinesis.
A In yeast, a signaling cascade (shown
on the right) from Cdc42p via the effector proteins Cla4p
and Bni1p leads to the formation of a septin ring (yeast
cell on the left shows a schematic representation of the
ongoing processes). Recruitment of the acto-myosin ring
involves the IQGAP-related protein Cyk1p/Iqg1p. Bud3
(and other proteins) is also recruited to the bud neck
to form a ring. Initially, single rings are formed. During
the dynamic phase initiated by the mitotic exit network
(MEN), ring splitting of septin and Bud3 rings occurs,
while the acto-myosin ring undergoes constriction. The
chitin synthase Chs3p is also localized to the septin ring
via a set of protein–protein interactions, and a primary
(by Chs2p) as well as secondary (by Chs3p) septum is
formed. B Hyphae in Ashbya gossypii allow the view of
different stages of septation, spatially separated along the
hypha. Close to the hyphal tip, single rings of septins,
Bud3p, and acto-myosin are formed. Dynamic events may
occur at a subapical septum, showing ring splitting and
acto-myosin contraction, while protein complexes at septal
sites in further subapical regions have been disassembled
upon septum completion. Note the different role of
Bud3p in A. gossypii that, in contrast to Saccharomyces
cerevisiae, is involved in recruiting Cyk1p to the septal
sites