Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281Network | 27.3333 | 0.01 | No | - | 4 | CaM | CaM
Pathway No. 283 | Network | 26.3333 | 0.09 | No | - |
| There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels. |
5 | CaM-PSD | CaM
Pathway No. 283 | Network | 26.3333 | 0.01 | No | - |
| There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels. |
6 | tot_CaMKII_cyt | CaMKII
Pathway No. 282 | Network | 22 | 0.09 | No | CaMKII-CaM CaMKII-thr286*-C aM CaMKII-thr286 CaMKII*** CaMK-thr305 CaMKII basal_CaMKII_ cyt
|
7 | CaMKII | CaMKII
Pathway No. 282 | Network | 20 | 0.09 | No | - |
| Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around 2.5% of protein in spine as a whole. This level is so high it is unlikely to matter much if we are off a bit. This comes to about 70 uM. |
8 | neurogranin | CaM
Pathway No. 283 | Network | 10 | 0.09 | No | - |
| Also known as RC3 and p17 and BICKS. Conc in brain >> 2 uM from Martzen and Slemmon J neurosci 64 92-100 1995 but others say less without any #s. Conc in dend spines is much higher than overall, so it could be anywhere from 2 uM to 50. We will estimate 10 uM as a starting point. Gerendasy et al JBC 269:35 22420-22426 1994 have a skeleton model (no numbers) indicating CaM-Ca(n) binding .... |
9 | neurogranin_PSD | CaM
Pathway No. 283 | Network | 10 | 0.01 | No | - |
| Also known as RC3 and p17 and BICKS. Conc in brain >> 2 uM from Martzen and Slemmon J neurosci 64 92-100 1995 but others say less without any #s. Conc in dend spines is much higher than overall, so it could be anywhere from 2 uM to 50. We will estimate 10 uM as a starting point. Gerendasy et al JBC 269:35 22420-22426 1994 have a skeleton model (no numbers) indicating CaM-Ca(n) binding .... |
10 | I1 | PP1_PSD
Pathway No. 286 | Network | 4 | 0.01 | No | - |
| I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM. |
11 | PP1-active_PSD | PP1_PSD
Pathway No. 286 | Network | 4 | 0.01 | No | - |
| Cohen et al Meth Enz 159 390-408 is main source of info conc = 1.8 uM in their study. Here we use about 2x this level because of high PSD levels of many proteins. In this model of weak coupling, this pool only acts on the AMPARs in the membrane, and not on CaMKII. |
12 | GluR23_M | AMPAR
Pathway No. 287 | Network | 3.5 | 0.01 | No | - |
13 | PDE1 | AC
Pathway No. 289 | Network | 2.5926 | 0.09 | No | - |
| CaM-Dependent PDE. Amount calculated from total rate in brain vs. specific rate. |
14 | temp-PIP2 | Shared_Object_ AMPAR_CaMKII_ weak_coupling Pathway No. 281Network | 2.5 | 0.09 | Yes | - | |
| This isn't explicitly present in the M&L model, but is obviously needed. I assume its conc is fixed at 1uM for now, which is a bit high. PLA2 is stim 7x by PIP2 @ 0.5 uM (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, which comes to 50 nM. Ref is Majerus et al Cell 37 pp 701-703 1984 Lets use a lower level of 30 nM, same ref.... |
15 | PP1-active_ CaMKII_PSD | PP1_CaMKII_PSD
Pathway No. 291 | Network | 2 | 0.01 | No | - |
| Cohen et al Meth Enz 159 390-408 is main source of info conc = 1.8 uM in their study, here it is almost the same. In this model of weak coupling between CaMKII and AMPAR, this phosphatase pool acts only on the CaMKII present in the PSD. |
16 | basal_CaMKII_ PSD | CaMKII_PSD
Pathway No. 292 | Network | 2 | 0.01 | No | - |
17 | basal_CaMKII_ cyt | CaMKII
Pathway No. 282 | Network | 2 | 0.09 | Yes | - |
18 | basal_CaMKII_ PSD_control | CaMKII_PSD
Pathway No. 292 | Network | 2 | 0.01 | Yes | - |
19 | tot_autonomous_ CaMKII | CaMKII
Pathway No. 282 | Network | 2 | 0.09 | No | CaMKII-thr286 CaMKII*** basal_CaMKII_ cyt
|
20 | act_CaMKII_cyt | CaMKII
Pathway No. 282 | Network | 2 | 0.09 | No | tot_CaM_CaMKII tot_autonomous_ CaMKII
|