Chemistry Reference
In-Depth Information
FIGURE 8.16
An overview of zinc transport and trafficking in the yeast S. cerevisiae. ZIP family transporters are shown in blue and CDF
family transporters are shown in red. Hypothetical transporters or known proteins from other families of transporters are shown in gray. The
Zap1 transcriptional activator, shown in black, is responsible for the upregulation of many target genes in zinc-limited cells. Zn
2
þ
in the vacuole
is likely bound by some ligand (L) to facilitate storage.
(From
Eide, 2006
.
Copyright 2006, with permission from Elsevier.)
Zrc1 is a Zn
2
þ
/H
þ
antiport,
3
allowing the zinc accumulation in the vacuole to be driven by the proton
concentration gradient generated by the vacuolar H
þ
-ATPase. The Cot1 protein may function in the same way.
The release of zinc to the cytosol is mediated by the Zip family member Zrt3. Within the vacuole, zinc may be
bound to organic anions. Vesicular storage sites for zinc may also exist in mammalian cells, where they have
been designated “zincosomes”, and such membrane-bound vesicles have also been observed in zinc-treated
yeast. There are almost certainly zinc transporters to supply the metal to mitochondria, and in the secretory
pathway, involving both the Golgi apparatus and the endoplasmic reticulum, there are also zinc transporters,
notably the Msc2/Zrg17 complex.
4.
Iron, copper, and zinc homeostasis in fungi
As we saw earlier (Chapter 7), S. cerevisiae has a variety of genes coding for proteins which are involved in iron
acquisition at the cell surface, and many of them are transcriptionally induced in response to low iron. The
high-affinity transport system (Fet3, Ftr1) contains a ferroxidase, which requires copper as a cofactor, and as
a consequence, genes that are involved in the trafficking and transport of copper to this Fet3 protein (Atx1 and
Ccc2, described later) are also regulated at the transcriptional level by iron. It is clear that high-affinity iron uptake
is seriously compromised by low levels of extracellular copper. Iron-dependent gene regulation in S. cerevisiae is
mediated by two transcription factors, Aft1 and Aft2 ('Activator of Ferrous Transport'). Under iron-limiting
conditions, Aft1 activates transcription of a specific set of genes involved in iron uptake, mobilisation of stored
iron, and metabolic adaption which occur under iron-limitation conditions. These include seventeen genes
involved directly or indirectly in iron uptake at the plasma membrane. Among these are both reductases Fre1 and
2, the high-affinity (Fet3, Ftr1) and low-affinity (Fet4) systems for free iron uptake, as well as the family of
transporters (Arn1 to Arn4) which cycle between the cell surface and an endosomal compartment, mediating ferric
siderophore uptake. It also regulates the expression of a number of other genes, including other cell surface
reductases, a mitochondrial iron transporter (Mrs4), and proteins involved in the biosynthesis of iron
e
sulfur
clusters(Isu1 and Isu2), and the three cell wall mannoproteins, FIT1, FIT2, and FIT3, which enhance retention of
ferric siderophores. Aft2 regulates the expression of an overlapping set of genes.
3. An antiport simultaneously transports two molecules (or in this case, ions) simultaneously in opposite directions.
