This is an assignment for an undergraduate course at Davidson College


The text below discusses the clustering of sec18 with other genes under certain environmental conditions.  sec18 is a protein
that mediates vesicular fusion between vacuolar fragments during mitosis and between ER and golgi vesicles during the
transport of proteins.  For a full report of the expression of sec18 in response to various environmental and cellular conditions,
go to this website and run a search with sec18
<http://genome-www4.Stanford.EDU/cgi-bin/SGD/expression/>.  The clustering should appear similar
to this for the clustering of sec18 with other genes in response to alpha factor.

I) Response to alpha factor

     The expression of sec 18 goes up very little in the presence of increasing alpha factor.  One would expect that since sec18 is
involved in fusion between vesicles of the ER and golgi it would follow that sec18 expression would go up in response to increasing alpha factor. It is known that the receptor for alpha factor is upregulated in response to increasing alpha factor.  The alpha-receptor is a tranmembrane protein that must go through the ER and golgi to approach the plasma membrane.

II) Response to DNA damaging agent

    sec18 does not respond drastically to DNA damaging agents.  Although there are other proteins that seem to change their
expression dramatically, one would not expect the expression of sec18 to change unless most of the proteins being induced
were going to be secreted or unless thos proteins were transmembrane proteins.  If the protein expression changed in favor of
cytosolic proteins, then sec18 would not have to be upregulated because protein traffic between the ER and the gologi would
either stay the same or decrease.

III) Expression of sec18 during the cell cycle.
  The expression of sec18 during the cell cycle in the microarray data at

<http://genome-www4.Stanford.EDU/cgi-bin/SGD/expression/> does not correlate with the literature
on sec18..  Sec18 is responsible for vacuolar fusion in the yeast daughter cell.  One would therefore expect sec18 expression to increase significantly in at lease one phase of cell division so as to mediate vacuolar fusion in the budding yeast daughter. Sec18 is not increased significantly however.  The only explanation for this would be that the quantity of sec18 stays relativelyconstant at an amount that can sufficiently mediate vacuolar fusion when the time is necessary.  Another question that remains is why sec18 would be downregulated during the cell cycle.  One possible reason for this would be that there comes a time when vesicular fusion could adversely affect the cell.  If all vacuolesfused together in S phase for example, then one daughter cell would not get the appropriate share of this organelle after division.

IV) Expression of sec18 during sporulation

    The data here indicate that sec18 expression is not changed that much during yeast sporulation.  However, a slight induction
idoes occur and would seem to be appropriate in that vesicular aggregation and fusion would have to occur to make sure the
haploid daughters received their complement of vacuoles.

V) Expression of sec18 in response to changing environmental conditions

    sec18 is variably induced and repressed in response to different environmental conditions.  One reason why sec18 would be
repressed in response to a changing environmental condition is that proteins in the ER change shape in response to varying
conditions.  In response to heat, for example, proteins can be unfolded and must reside in the ER so they can refold in their
proper confomration (Simola et al., 2000).  Trehalose mediates the proper refolding of proteins in the ER.  When a return to
proper folding occurs for proteins in the ER, sec18 is downregulated so that ER vesicles cannot fuse with the golgi.  If sec18
did mediate fusion between the ER and the golgi while proteins were misfolded, proteins would be transported to cellular
locations only to be non-functional.  Protein structure indeed equals function! Conversely, sec18 may be upregulated to send
proteins to the plasma membrane in cases where transmembrane proteins are denatured as a result of the environmental
conditions.  The proteins transported to the plasma membrane with the help of sec18 may replace their misfolded counterparts
or aid the recovery of those proteins that are misfolded.  Such a scenario could explain the inductions of sec18 in response to
changing environmental conditions.

VI) Expression of sec18 in response to histone depletion

    sec18 is  downregulated in response to histone depletion.  This makes intuitive sense since histones maintain the integrity
ofDNA.  When the structure of DNA risks being disrupted by the loss of histones, protein synthesis should shut down since
translated products may contain amino acid irregularities.  So as to stop protein traffic, sec18 would naturally be downregulated
so that altered proteins made by mistake do not get transported to other parts of the cell.
VII) Other expression patterns of sec18
    The expression pattern of sec18 does not change drastically during a diauxic shift from an aerobic to an anaerobic
environment.  sec18 neither changes its expression significantly in tup deletions or Yal overexpression.

                                         References Cited

1)      Saccharomyces Genome Database [online database]. Available from:
<http://genome-www4.Stanford.EDU/cgi-bin/SGD/expression/> Accessed 2001 Oct17
2)      Simola et al. (2000).  Trehalose is required for heat-denatured proteins in the yeast ER but not for membrane traffic
functions after severe heat stress.  Molecular Microbiology; 37 (1); 42-53

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