人體病原真菌隱球菌生殖,菌絲生長及致病分子機制之探討(III)
Date Issued
2004
Date
2004
Author(s)
DOI
922311B002094
Abstract
Cryptococcus neoformans, an
opportunistic human fungal pathogen, causes
the life-threatening meningoencephalitis
mainly in individuals with compromised
immune functions. Studies of the
pathogenesis in C. neoformans have revealed
several important virulence factors such as
2
capsule, melanin, ability to grow at 37 ℃ or
higher temperature, and interestingly the
mating type locus. The MATα locus of C.
neoformans has been identified and
characterized. It has unusual large size of
over 100 kb and contains more than 20 genes.
Three copies of pheromone precursor genes
are identified in the MATα locus.
Characterization of pheromone gene triple
deletion mutant strains suggested an
autocrine signaling loop may function and
contribute to the virulence of the MATα cells
(Shen et al., 2002). The purpose of this
proposal is to characterize the components in
the pheromone response pathway of C.
neoformans serotype D strain and further
address how mating type locus regulates the
virulence and how the autocrine signaling
loop functions in C. neoformans.
To further address the role of
pheromones in the signaling loop, we have
identified the STE6 homologue, the S.
cerevisiae a-factor exporter, in the C.
neoformans genome and begun to dissect its
function. By disrupting the STE6, we found
that ste6 mutants in either MATα or MATa
background showed partially impaired
mating function. However, when ste6 MATα
and MATa mutants bilaterally cross with each
other, the mating process was completely
abolished. Surprisingly, MATα ste6 mutant
does not exhibit a defect in haploid fruiting,
which implicates that the pheromone
molecules could induce the signaling
response intracellularly in MATα cells. We
conclude that Ste6 is evolutionally conserved
for mating and is not required for
monokaryotic fruiting in C. neoformans.
Additionally, we have also characterized the
α and β subunits of heterotrimeric G
protein complex. Phenotypic characterization
of respective mutants suggests that they
possibly form the G protein complex
functioning in the upstream of the pheromone
response pathway. G protein α subunit gene,
GPA3, negatively regulates mating and
haploid fruiting in C. neoformans. G protein
βsubunit gene, GPB1, positively regulates
mating in C. neoformans.
Subjects
Cryptococcus neoformans
pheromone response pathway
pheromone
pheromone transporter
heterotrimeric GTP binding
protein α and ß subunit
protein α and ß subunit
Publisher
臺北市：國立臺灣大學植物病理與微生物學系暨研究所
Type
other
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