User:Etienne Robillard/Notebook/NMDA dependent cell adhesion
Mo calcium, mo visual hallucinations
An essay on the role of the Integrin beta-3 protein (ITGB3) in Ca2+-dependent orthogonal riboswitches.
In the study of calcium-mediated (Ca2+) neuronal receptors (NMDA and GABA mostly), the relevance of Ca2+-dependent ligands (ie: calmodulin) may hold important factors in the morphogenesis of psychological brain disorders and the pathogenesis of the Alzheimer disease, a important phenotype in the understanding of GPCR-mediated brain mutations. Hence a proper understanding of the polypyrimidine tract binding protein-1 (PTBP1) dependent signaling pathway may reveal new insights in the functions and features of the integrin beta-3 protein as a cell-adhesive (and voltage-gated!) neural substrate for long-term axon and neuronal growth. 
A integrin beta3 mutant polypeptide lacking the PTBP1 gene ?
- A pyrimidine-rich associated polypeptide complex is best known as a "protein".
- A e.coli K12 derived auxotrophic restriction enzyme system may be the key red heering in understanding protein over-expression factors in the transcription of mRNA.
- Dude where's my calcium?: Zinc/Leucine/Glycine/Serine (Rho, GNAT, etc) -> KEY Calcium/Magnesium (Ca2+/Mg2+) mediated cell adhesion amino acids; phosphatase-like (transferase) family members...
- Neural (Voltage-gated) ligand expression possible side-effect may include novel psychotic behavior, especially if remotely activated with electromagnetic (RF) signals under 2.45 GHz ? -- Check this.
- "horn" directed mutagenesis: too difficult to realize in vivo? -- Check this!
Going a bit further...
- Explain dna methylation and role of 30C6HSL, a keto-ester, in the upregulation of N-Methyl-D-Aspartate receptor and Calcium channel blockers
- summarly define how a calcium channel blocker 'block' (disrupt) GABA receptor from processing visual signals properly in the fore-brain (ie: hippocampus) through a signal transduction cascade...
- What is primary difference between a putative and non-putative gene?
- Erbb Signaling Pathway: http://www.genome.jp/dbget-bin/www_bget?pathway:map04012 Look for "CAMK" on this map and which conclusions may you draw from its interactions (Cross-talking) with erbb2? Is erbb2 a promoter or a repressor of Calcium-dependent adhesion (and why)?
- On Hill coefficient (Kd) measurement and analysis:
- In short, the Hill coefficient is a statistical tool (function) to measure binding (adhesion) variance when information about a system is poor.
- As pointed out by Cornish-Bowden and Koshland (1975), the ‘logit’ plot in pharmacology is a plot identical to the Hill plot, and formally equivalent to Nernst's plot of redox electrochemistry (Reed & Berkson 1929, their example 5; Malmstrom 1974). The logit plot is also equivalent to the gating transitions of voltage dependent ion channels (Yifrach 2004). See Section 10.3.9 for more on the relationship between the Nernst and the Hill equations. http://journals.sfu.ca/coactionbks/index.php/Bindslev/article/viewArticle/14/75
Case study: Focus on Hemagglutinin binding factors
- Review this Free PMC here. Can you identify the factors which makes the HA protein clump or can you postulate the role and significance of Ca2+ signaling pathway in the viral coating of the H. influenza virus ? Recall that the Hemagglutinin protein is solely required for the H. influenza virus to attach into its host and begin an unwary invasion on the immune system.
- Note 1 (HA cleaving factors): "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs." 
- Based on this comment above, can you postulate how unwary HA infections may silently avoid immune-specific detection by the host ??
Case study: Focus on Alzheimer phenotype
- CAMK -- Alcoholism*, Learning (memory), LTP
- NMDAR -- Alcoholism*, Alzheimer, LTP
- NMDAR -> CREB2 http://www.genome.jp/dbget-bin/www_bget?hsa:468
- Proteins and enzymes:
- cAMP-dependent protein kinase A (C-alpha): http://www.uniprot.org/uniprot/P17612
- cAMP-dependent protein kinase A (C-beta) : http://www.uniprot.org/uniprot/P22694
- Histone-lysine N-methyltransferase (SETD8) http://www.uniprot.org/uniprot/Q9NQR1 OMIM
- E-cadherin (CDH1) http://www.uniprot.org/uniprot/P12830 OMIM
- Wnt3 (also known as the Ca2+ pathway, aka a Voltage-gated ion channel...) http://www.uniprot.org/uniprot/P56703 pathway
- c-Src proto-oncogene: http://www.uniprot.org/uniprot/P12931
- By organism:
- H. sapiens (EC 22.214.171.124, PTEN-Induced Putative Kinase 1) http://www.genome.jp/dbget-bin/www_bget?hsa:65018 BRENDA
- H. sapiens (EC 126.96.36.199, CaM kinase II, CamKII) http://www.genome.jp/dbget-bin/www_bget?ec:188.8.131.52
- H. sapiens (EC 184.108.40.206, SETD8) http://www.genome.jp/dbget-bin/www_bget?hsa:387893
H. sapiens (ITGB2) : http://www.genome.jp/dbget-bin/www_bget?hsa:3689 OMIM (note the chromosome location and the annotated phenotype)
- H. sapiens (NMDAR1) : http://www.genome.jp/dbget-bin/www_bget?hsa:2902
Integrins(Ketamine), S1P, pyrimidine (?), calcium, glutamine, NMDA, hippocampus, calmodulin, PTBP1, neuropeptides, b-secretase (BACE), NMDAR, NMDAR1
For next time!
- Review Calcium and GABA signaling?
- IFP as a flow calibration mesure to visualize the impact of Ketamine on neurocognitive functions via Remote triggered smart phones (iphone4 type tablets)
- Ketamine (Arylcyclohexylamine) induced beta-amyloids APP (Alzheimer Disease) plaque aggregation
- Review role of PLP (pyridoxal-5-phosphate) in the intermediate synthesis of Schiff bases (pKa=11). Notice the presence
of ketimine in the reaction and the -rC=N alpha-hydrogen linkage. Review acidity of alpha-Hydrogens bonds here
- Rhodopsin - Rho/GTPase specific AI inducers: Rhodopsin etc.
- c-Src specialized kinase (SH2/SH3 domain, PH domain, etc)
- MAPK <-> c-Src domain interactions and cross-talk, ie integrins mediated cross-talking, see: EGFR
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