This is an assignment for an undergradutate course at Davidson College

Expression of sec18 changes in reponse to changing cellular environments. Below are listed microarrays that clustered sec18 expression with various cellular environments. Explanations for such expression follow the microarrays.

Expression of Sec18 and its cluster at different concentrations of alpha factor

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YDL164C	CDC9	nucleotide-excision repair*	DNA ligase (ATP)	replication fork
YGL188C		biological_process unknown	molecular_function unknown	not yet annotated
YER142C	MAG1	not yet annotated	DNA-3-methyladenine glycosidase II	not yet annotated
YPL065W	VPS28	not yet annotated	not yet annotated	not yet annotated
YPR072W	NOT5	transcription	not yet annotated	not yet annotated
YDR205W	MSC2	biological_process unknown	molecular_function unknown	not yet annotated
YJR042W	NUP85	mRNA-nucleus export*	structural protein	nuclear pore
YER056C-A	RPL34A	protein biosynthesis	structural protein of ribosome	cytosolic large ribosomal (60S) subunit
YBR144C		biological_process unknown	molecular_function unknown	not yet annotated
YGR182C		biological_process unknown	molecular_function unknown	not yet annotated
YLR039C	RIC1	transcription regulation, from Pol II promoter*	molecular_function unknown	nucleus
YLR038C	COX12	not yet annotated	cytochrome-c oxidase	not yet annotated
YOR275C		biological_process unknown	molecular_function unknown	not yet annotated
YJL102W	MEF2	protein synthesis elongation	translation elongation factor	mitochondrion
YMR184W		biological_process unknown	molecular_function unknown	not yet annotated
YAL067C	SEO1	not yet annotated	not yet annotated	not yet annotated
YPR151C		biological_process unknown	molecular_function unknown	not yet annotated
YKL161C		biological_process unknown	not yet annotated	not yet annotated
YKL006C-A	SFT1	intra Golgi transport	v-SNARE	Golgi membrane
YMR230W	RPS10B	protein biosynthesis	structural protein of ribosome	cytosolic small ribosomal (40S) subunit

As can be seen here 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 golgo to approach the plasma membrane. Figures were obtained from: <http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Timed response of sec18 to alpha factor

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YDL087C	LUC7	mRNA splice site selection	small nuclear ribonucleoprotein	cellular_component unknown
YCL042W		biological_process unknown	molecular_function unknown	not yet annotated
YML131W		biological_process unknown	molecular_function unknown	not yet annotated
YBR046C	ZTA1	biological_process unknown	molecular_function unknown	not yet annotated
YML058C-A		biological_process unknown	molecular_function unknown	not yet annotated
YGL180W	APG1	autophagy	protein serine/threonine kinase	cytosol
YBL064C		biological_process unknown	molecular_function unknown	not yet annotated
YHR079BC
YMR097C		biological_process unknown	molecular_function unknown	not yet annotated
YDR442W		biological_process unknown	molecular_function unknown	not yet annotated
YJR078W		biological_process unknown	molecular_function unknown	not yet annotated
YDR368W	YPR1	biological_process unknown	molecular_function unknown	not yet annotated
YOR177C	MPC54	biological_process unknown	molecular_function unknown	not yet annotated
YMR297W	PRC1	not yet annotated	carboxypeptidase C	not yet annotated
YJL021C
YOL098C		biological_process unknown	molecular_function unknown	not yet annotated
YGR243W		biological_process unknown	molecular_function unknown	not yet annotated
YKL039W	PTM1	biological_process unknown	molecular_function unknown	not yet annotated
YJL082W	IML2	not yet annotated	molecular_function unknown	not yet annotated
YLR225C		biological_process unknown	molecular_function unknown	not yet annotated

Expression in response to alpha-factor for SEC18/YBR080C

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Although the table here would indicate that sec18 expression increases over time in response to alpha factor, as is expected, the microarray data are ambiguous. Induction is not evident because the color change is not dramatic. The figres here were obtained from :<http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Response of sec18 and its cluster to DNA damaging agents

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YNR034W	SOL1	not yet annotated	molecular_function unknown	not yet annotated
YCL057W	PRD1	not yet annotated	saccharolysin	not yet annotated
YJR059W	PTK2	polyamine transport	not yet annotated	not yet annotated
YBR260C	RGD1	biological_process unknown	not yet annotated	not yet annotated
YGL190C	CDC55	protein biosynthesis*	protein phosphatase type 2A	protein phosphatase type 2A

The response of sec18 to DNA damaging agents here is not dramatic. Although it would be expected that protein and RNA expression would change in response to a DNA damaging agents, this does not necessarily mean that protein expression would require more traffic between the ER and the golgi. If protein expression changed in favor of cytosolic proteins, there would be no need for a change in sec18 expression. The figres here were obtained from < http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Expression of Sec18 during the cell cycle

Name	Score	Peak
SEC18	0.471
Reference Genes
CLN2	10.9	G1
HTA1	10.68	S
CLB4	3.08	G2
SWI5	6.726	M
ASH1	11.8	M/G1

Plot of SEC18 (YBR080C)

The data here do not correlate nicely with the literature on sec18 in my opinion. 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 here however. The only explanation for this would be that the quantity of sec18 stays relatively constant 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 vacuoles fused together at any one time, then one daughter cell would not get the appropriate share of this organelle. The figures here were obtained from this website: < http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Expression of sec18 during the diauxic shift

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YML046W	PRP39	mRNA splicing	not yet annotated	not yet annotated
YGR229C	SMI1	not yet annotated	not yet annotated	not yet annotated
YHR027C	RPN1	ubiquitin-dependent protein degradation	multicatalytic endopeptidase	19S proteasome regulatory particle
YMR130W		biological_process unknown	molecular_function unknown	not yet annotated
YMR020W	FMS1	not yet annotated	molecular_function unknown	not yet annotated
YBR198C	TAF90	transcription initiation, from Pol II promoter*	general RNA polymerase II transcription factor	TFIID complex*
YER160C
YLR386W		biological_process unknown	molecular_function unknown	not yet annotated
YML069W	POB3	chromatin modeling*	molecular_function unknown	nucleus
YDR381W	YRA1	mRNA processing	not yet annotated	not yet annotated
YLR052W	IES3	biological_process unknown	molecular_function unknown	not yet annotated
YPR129W	SCD6	not yet annotated	not yet annotated	not yet annotated
YBR082C	UBC4	stress response*	ubiquitin conjugating enzyme	cellular_component unknown
YGR261C	APL6	not yet annotated	not yet annotated	not yet annotated
YMR285C	NGL2	biological_process unknown	molecular_function unknown	cellular_component unknown
YER122C	GLO3	ER to Golgi transport*	ARF GTPase activator	ER-Golgi intermediate compartment
YNR076W	PAU6	biological_process unknown	not yet annotated	not yet annotated
YCR027C	RSG1	biological_process unknown	not yet annotated	not yet annotated
YPR118W		biological_process unknown	molecular_function unknown	not yet annotated
YJL197W	UBP12	deubiquitylation	ubiquitin-specific protease	cellular_component unknown

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The data here indicate that sec18 expression does not appreciably change during the diauxic shift. This figure was obtained from <http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Expression of sec18 during sporulation

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YGR223C		biological_process unknown	molecular_function unknown	not yet annotated
YMR032W	HOF1	cytokinesis	cytoskeletal protein binding protein	cytokinetic ring (sensu Saccharomyces)
YOL095C	HMI1	biological_process unknown	not yet annotated	not yet annotated
YPL206C		biological_process unknown	molecular_function unknown	not yet annotated
YGL024W		biological_process unknown	molecular_function unknown	not yet annotated
YMR179W	SPT21	transcription	not yet annotated	not yet annotated
YKL132C	RMA1	not yet annotated	folylpolyglutamate synthase	not yet annotated

Expression during sporulation for SEC18/YBR080C

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The data here indicate that sec18 expression is not changed that much during yeast sporulation. However, a slight induction in the first two hors 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 and other organelles. The figure here was obtained from <http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

Expression of sec18 in response to environmental changes

Orf		Gene				Process		Function		Component
YBR080C		SEC18				ER to Golgi transport*		adenosinetriphosphatase		cytoplasm*

The data here do not represent the full figure from < http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>. A more complete picture of this information would show that 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). When this occurs, sec18 is downregulated so that ER vesicles cannot fuse with the golgi. 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.

Orf	Gene	Process	Function	Component
YBR080C	SEC18	ER to Golgi transport*	adenosinetriphosphatase	cytoplasm*
YBR069C	TAT1	transport	amino acid permease	not yet annotated
YDR158W	HOM2	not yet annotated	aspartate-semialdehyde dehydrogenase	not yet annotated
YGR230W	BNS1	biological_process unknown	molecular_function unknown	not yet annotated
YCR082W		biological_process unknown	molecular_function unknown	not yet annotated
YGR105W	VMA21	vacuolar acidification	not yet annotated	not yet annotated
YML027W	YOX1	biological_process unknown	not yet annotated	not yet annotated
YBL002W	HTB2	not yet annotated	not yet annotated	nucleosome
YDR133C		biological_process unknown	molecular_function unknown	not yet annotated
YBL030C	PET9	ATP/ADP exchange	ATP/ADP antiporter	mitochondrial inner membrane
YGR181W	TIM13	mitochondrial translocation	protein transporter	mitochondrial intermembrane space
YJL208C	NUC1	DNA recombination	endodeoxyribonuclease*	mitochondrial inner membrane
YCR004C	YCP4	biological_process unknown	molecular_function unknown	not yet annotated
YHR208W	BAT1	not yet annotated	branched-chain amino acid aminotransferase	not yet annotated
YNL056W		biological_process unknown	molecular_function unknown	not yet annotated
YDR297W	SUR2	sphingolipid metabolism	sphingosine hydroxylase	endoplasmic reticulum
YDR381W	YRA1	mRNA processing	not yet annotated	not yet annotated
YNL231C	PDR16	not yet annotated	molecular_function unknown	not yet annotated
YBR068C	BAP2	transport	not yet annotated	not yet annotated
YML119W		biological_process unknown	molecular_function unknown	not yet annotated
YPL190C	NAB3	mRNA splicing	not yet annotated	not yet annotated

Expression of sec18 in response to histone depletions

Expression in response to histone depletion for SEC18/YBR080C

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The data here indicate that sec18 is eventually downregulated in response to histone depletion. This makes intuitive sense since histones maintain the integrity of DNA. 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 localize to other parts of the cell. The figures here were obtained from < http://genome-www4.stanford.edu/cgi-bin/SGD/expression/expressionConnection.pl>

References Cited

1) Saccharomyces Genome Database [online database]. Available from: http://genome-www.stanford.edu/Saccharomyces/ Accessed 2001 Oct 17

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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