Growth, Differentiation and Sexuality

90 J.P. Latgé and R. Calderone
signalling (Matheos et al. 1997). In addition to the
up-regulation of the Rlm1p- and STRE-controlled
genes, Boorsma et al. (2004) showed an additional
response with Sko1p, a downstream regulator of the
HOG pathway. The cell wall compensatory mechanism
to process cell wall perturbations integrates
then the PKC/SLT, the global stress response pathway
mediated by the Msn2p, the transcription factor
downstream of the HOG pathway gene product,
and the Ca 2+ /calcineurin-dependent pathway.
Direct molecular interactions between these different
transduction cascades have been suggested but
never demonstrated as yet.
Although the pheromone and RAS/cAMP pathways
are also somehow associated with cell wall
biosynthesis (Daniels et al. 2003; Calcagno et al.
2004; Fitch et al. 2004; Nelson et al. 2004), these
pathways are not detailed here because they do not
play a direct role in cell wall modifications (for
a review of these different pathways, see Brown
2002, and Palacek et al. 2002). Only discussed below
are the PKC pathway, the HOG pathway, and
the Ca 2+ /calcineurin-dependent pathway. Our understanding
of the role of each pathway in modifyingcellwallcompositionisbasedmainlyonthe
analysis of the phenotype of mutants obtained by
gene disruption of members of each signalling cascade.
Fig. 5.11. The compensatory cell wall mechanism
of fungi. A variety of stress factors
cause changes in the cell wall, including
an increase in chitin, changes in the ratios
of β-1,3/β-1,6, shifts in the association of
mannoproteins with glucans, and a redistributionofcellwallsynthesistoamore
global distribution, rather than an association
with only the growing part of cells. The
various cell wall polysaccharides coded are
indicated with shading of different intensities
B. Signal Transduction Cascades Responsible
for Major Cell Wall Compensatory
Mechanisms
The three major signal transduction cascades
involved in cell wall repairs are schematised in
Fig. 5.12.
1. The HOG MAP Kinase Pathway
The HOG MAPK pathway (hyperosmolarity
glycerol) was originally described in S. cerevisiae
and shown to be essential for adaptation of the
organism to hyperosmotic stress (O’Rourke et al.
2002). The proteins which are upstream of the
MAPKKK, MAPKK and MAPK (Hog1p) signal
transduction pathway proteins are two-component
proteins. In S. cerevisae, the phosphorylation
of the membrane-associated histidine kinase
(HK) protein (Sln1p) results in phosphotransfer
to another HK intermediate (Ypd1p), and then
Ypd1p transfers its phosphate to an aspartate
of the response regulator (RR) protein, Ssk1p,
which acts as a transcriptional regulator of genes
associated with a specific adaptive phenotype
(Fig. 5.12; Tatebayashi et al. 2003).
In C. albicans, there is a total of five histidine
kinases and response regulator proteins, includ-