Protein dilution/synthesis due to cell growth

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Contents 1 Protein Dilution and Synthesis 1.1 Dilution 1.2 Pheromone Synthesis 1.3 Dig1 Synthesis 1.4 Dig2 Synthesis 1.5 Far1 Synthesis 1.6 Fus3 Synthesis 1.7 Gpa1 Synthesis 1.8 Kss1 Synthesis 1.9 Msg5 Synthesis 1.10 Ptp Synthesis 1.11 Sst2 Synthesis 1.12 Ste2 Synthesis 1.13 Ste4 Synthesis 1.14 Ste5 Synthesis 1.15 Ste7 Synthesis 1.16 Ste11 Synthesis 1.17 Ste12 Synthesis 1.18 Ste20 Synthesis 1.19 Yck Synthesis

Protein Dilution and Synthesis

All of the proteins in the cell are effectively lost at a rate that is equal to the growth rate of the cell. This is due to the dilution of the cell. As the volume increases during growth, the concentration of the individual proteins would decrease unless they were produced at a commensurate rate. This loss (and balancing synthesis) due to dilution may be insignificant for proteins with a high turnover rate, or may be the major form of loss for stable proteins.

We will apply a dilution rate (which is the same as the growth rate) for all complexes in the cell. Individual proteins will be synthesized at a rate that will maintain their expected concentration. Proteins whose degradation is specifically accounted for elsewhere in this model also have a corresponding synthesis rate that compensates for that means of degradation. To balance the dilution rate, the synthesis rates must be kdilutionsynth = kdilution * Protein_tot, where Protein_tot is the total concentration of the protein in the cell.

For pheromone-induced synthesis of proteins, please see Ste12 mediated protein synthesis. When Ste12 mediated protein synthesis is included in a model, the synthesis of several proteins through the reactions specified on this page, together with synthesis of these proteins through basal pathway activation of Ste12 (in the absence of pheromone), should balance the dilution rate. So when Ste12 mediated protein synthesis is included in a model, kdilutionsynth should be decreased by the amount of each protein's synthesis that occurs through basal activation of Ste12. This cannot be determined a priori because the basal activation of Ste12 in unknown. Dig2, Far1, Fus3, Msg5, Ptp, and Ste12 synthesis specified on this page must be decreased when Ste12 mediated protein synthesis is included in a model. Gpa1, Sst2, and Ste2 synthesis is also regulated by Ste12, but their synthsis is decreased elsewhere to account for this effect. See Gpa1 synthesis/degradation, Sst2 synthesis/degradation and Ste2 synthesis/endocytosis/degradation.

For each of the reactions below, the dummy species Cell used because BioNetGen requires at least one species on each side of reaction.

Dilution

{MatchOnce}* + Cell -> Cell

• The dilution rate is kdilution

• In order for the dilution reaction to work correctly, we need to include the statement exclude_reactants(1,Cell)

Pheromone Synthesis

It is important to note that pheromone is not actually synthesized by the cells that are responding to pheromone (at least not the same pheromone). This reaction is important to balance the artificial loss of pheromone due to dilution. Because pheromone is actually extracellular not intracellular like all the other species in the model, the concentration of pheromone should not be affected by cell growth. Since we model dilution of all complexes, including those containing pheromone, we have to compensate by addition pheromone back into the system. But note that this reaction is for modeling purposes, and does not actually represent the synthesis of pheromone

Cell -> Cell + Pheromone(Ste2_site)

• The "synthesis" rate (note again, this is not really synthesis) is kdilutionsynth_pheromone

Dig1 Synthesis

Cell -> Cell + Dig1(Ste12_site, MAPK_site, PO4_site~none)

• The synthesis rate is kdilutionsynth_Dig1

Dig2 Synthesis

Cell -> Cell + Dig2(Ste12_site, MAPK_site, PO4_site~none)

• The synthesis rate is kdilutionsynth_Dig2

Far1 Synthesis

Cell -> Cell + Far1(MAPK_site, S87~none, T306~none)

• The synthesis rate is kdilutionsynth_Far1

Fus3 Synthesis

Cell -> Cell + Fus3(docking_site, T180~none, Y182~none)

• The synthesis rate is kdilutionsynth_Fus3

Gpa1 Synthesis

Cell -> Cell + Gpa1(Ste2_site, Ste4_site, nucleotide~GDP)

• The synthesis rate is kdilutionsynth_Gpa1

Kss1 Synthesis

Cell -> Cell + Kss1(docking_site, T183~none, Y185~none)

• The synthesis rate is kdilutionsynth_Kss1

Msg5 Synthesis

Cell -> Cell + Msg5(MAPK_site)

• The synthesis rate is kdilutionsynth_Msg5

Ptp Synthesis

Cell -> Cell + Ptp(MAPK_site)

• The synthesis rate is kdilutionsynth_Ptp

Sst2 Synthesis

Cell -> Cell + Sst2(Ste2_site, MAPK_site, S539~none)

• The synthesis rate is kdilutionsynth_Sst2

Ste2 Synthesis

Cell -> Cell + Ste2(Pheromone_site, Gpa1_site, Sst2_site, Yck_site, S338_S339~none)

• The synthesis rate is kdilutionsynth_Ste2

Ste4 Synthesis

Cell -> Cell + Ste4(Gpa1_site, Ste5_site, Ste20_site)

• The synthesis rate is kdilutionsynth_Ste4Ste18

Ste5 Synthesis

Cell -> Cell + Ste5(Ste5_site, Ste4_site, Ste11_site, Ste7_site, MAPK_site)

• The synthesis rate is kdilutionsynth_Ste5

Ste7 Synthesis

Cell -> Cell + Ste7(Ste5_site, MAPK_site, S359_T363~none)

• The synthesis rate is kdilutionsynth_Ste7

Ste11 Synthesis

Cell -> Cell + Ste11(Ste5_site, MAPK_site, S302_S306_T307~none, Feedback_PO4~none)

• The synthesis rate is kdilutionsynth_Ste11

Ste12 Synthesis

Cell -> Cell + Ste12(Dig1_site, Dig2_site, MAPK_site)

• The synthesis rate is kdilutionsynth_Ste12

Ste20 Synthesis

Cell -> Cell + Ste20(Ste4_site, Ste11_site)

• The synthesis rate is kdilutionsynth_Ste20

Yck Synthesis

Cell -> Cell + Yck(Ste2_site)

• The synthesis rate is kdilutionsynth_Yck