Question

Question 3 A 48-year old woman presents to the Psychiatric Clinic where you are working. She has been suffering from memory loss and has lost her way home several times during the past week. During your conversation she explains that she lives alone, and had noticed that she was having problems with smelling food when it had spoiled, so she found herself throwing out her food just because she couldn't remember when she put it in the fridge, and she couldn't smell it. Being a card-carrying G-protein-coupled receptor biologist you decide to determine if she has normal olfactory receptors. You sequence 10 of her receptors and based on known sequences you can confirm that these are indeed GPCRs. You find the following conserved amino acids between all 10 GPCRs: LHTPMY AYDRYVAIC FSTCSSH PMLNPE Given the amino acid sequences, what predictions can you make regarding the likelihood that all 10 GPCRs are olfactory receptors? (5 points) How would you determine if her pattern of loss of olfactory function was likely to correlate with dementia? (5 points) In class we discussed ectopic expression of olfactory receptors, what tissues could express olfactory receptors ectopically that could affect memory (5 points)? What would be the mechanism of dementia (5 points)?

Answer 1

GPCRs charecterized by 7 transmembrane domains..Olfactory receptors from GPCRs by various conserved amino acids motifs, that is LHTPMY motif in the first intracellular loop, MAYDRYVAIC motif in the end of transmembrane (TM) domain 3 (TM3), short SY motif at the end of TM5,an FSTCSSH stretch at the beginning of TM6 and PMCNPF in TM7,..These all sequence different from spices to identify or genes from many genomes..activated OPs signal by Gaolf which stimulates adenylyl cyclase type III leads to more cAMP concentration and opening of calcium ( CNG ) channel..

Odorant receptors (OR) inhibits plasma membrane M7, fusion protein to assess plasma membrane and functioning of M7, in heterogeneous cells in olfactory sensory neurones (OSNs)..aminoacids not found in trafficking non - OR GPCR family..hydrophobic residues than non-OSN expressed amino receptors OR protein, prevent functional expression of ORs to the plasma membrane in heterogeneous cells..

When there is impaired olfactory function often coorelated with mild cognitive impairments ( MCI) and Alzheimer's Disease(AD)..neurogeneration effect on brain that stop the process of sense of smell, there will be less ability to sense the smell..it may also lead vascular dementia..