Lecture 6 Flashcards
(22 cards)
A bunch of our senses are mediated through what kind of signaling pathway?
GPCR signaling pathways
For a lot of signaling pathways for our senses, there is going to be a lot of ion channels mediated by second messengers. Why?
Ion channels are used for action potentials which transmit the sensory input from your environment into signals which reach your brain
What does rhodopsin act as a receptor for? Where is rhodopsin found? How is the signal received by rhodopsin relayed into the brain?
Rhodopsin is a light receptor. Rod and cone cells are the 2 cells that respond to light. Rhodopsin is found in membranous disks within rod and cone cells. The signal is relayed to the brain through synapsing of the rod cell to a neuron.
Inactive rhodopsin has a molecule of what bound at its active site? What happens when light of a certain wavelength is absorbed by this molecule?
Inactive rhodopsin has a molecule of 11-cis-retinal bound at its active site. When light of a certain wavelength is absorbed by that, the light causes a cis-trans isomerization of the retinal. This change is enough to cause a change in the conformation of the receptor, which causes the dissociation of the G-alpha protein subunit from the G-beta-gamma and initiate the signaling cascade responsible for converting photons into chemical signals - allowing us to be able to see light.
How do cone cells allow us the ability to see color? What structural feature is different amongst different cone cells which allows us to be able to see different colors?
Different forms of rhodopsin proteins have different forms of retinal within them. As a result of the differences in conjugation, this allows different forms of retinal to absorb different wavelengths of light. Combinations of these different forms of retinal allows us to have colored vision.
Explain how the activation of rhodopsin and the transducin subunit leads to the transmission of a nerve signal to the brain.
1) Light activated cis-trans conversion of 11-cis-retinal and this activates rhodopsin.
2) Rhodopsin allows for the activation of G-protein where GDP is switched for GTP on transducin and this dissociated T-GTP-alpha from T-beta-gamma.
3) T-GTP-alpha activates phosphodiesterase (PDE) by removing its inhibitory subunit.
4) Active PDE decreases [cGMP] levels to close the cation channels
5) Due to the lack of Na+ and Ca++ into the cell, the membrane is hyperpolarized and this signal is sent to the cell.
How does the receptor recover from the rhodopsin signals and respond to a new stimulus?
Low levels of Ca++ allows for the activaition of guanylyl cyclase which makes more cGMP, allowing the cation channel to reopen and the membrane potential goes back to -70 MV.
T-beta-gamma recruits rhodopsin kinase (responsible for phosphorylation of c-terminal domain of rhodopsin.) The phosphorylated rhodopsin will recruit Arrestin to bind to the receptor and pull it into the cell (hiding from being activated)
Why does it take time for our photoreceptors to recover?
Receptor are bleached from the sunlight.
Explain the pathway that allows us to generate a nerve impulse in response to a smell.
1) Odorant binds to the olfactory receptor or a binding protein that carries it to the OR.
2) The activated OR catalyzes the GDP-GTP exchange on a G-protein and causes the dissociation of alpha and beta-gamma.
3) G-alpha-GTP activates adenylyl cyclase and increases [cAMP.]
4) cAMP-gated cation channels open and Ca++ enters, raising internal Ca++.
5) The efflux of Cl- depolarizes the cell, sending a signal to the brain.
How is the olfactory receptor inactivated? What else occurs to ensure that we do not respond to the same odorant?
The influx of calcium from the cilia will reduce the affinity of the cation channel to cAMP. Now cAMP will not bind as well to the channel. This decreases the sensitivity to the cell. (Ca++ is preventing cAMP from binding to the channel)
1) G-alpha will hydrolyze the GTP that it has bound to GDP and a phosphodiesterase will breakdown cAMP.
2) Phosphorylation of the olfactory receptor will occur on the C-terminal end, thus allowing for the recruitment of some arrestin protein which prevents the receptor from working.
3) The odorant is removed from the receptor by metabolism and the pathway is now shut off.
The pathway will reset (dephosphorylation of the receptor and unbinding of the arrestin) so that we can smell the same smell again.
Explain the pathway which allows the generation of a nerve impulse in response to taste.
1) The respective molecule binds to the receptor(sweet to sweet, sour to sour, etc.), activating the G-protein gustducin.
2) This allows for the swap of GDP to GTP and dissociation of g-alpha and g-beta-gamma. G-alpha binds to adenylyl cyclase, raising [cAMP]
3) cAMP will activate PKA.
4) Activated PKA will phosphorylate a potassium channel to cause the potassium channel to close.
5) Efflux of potassium is reduced and this depolarizes the cell to send a signal to the brain.
How can we taste a wide range of flavors when we eat?
Part of the food particles end up in the nasal cavity and our brain puts smell and taste together.
What different taste receptors are coupled but produce different tastes after binding their specific ligands. How are their signaling pathways interconnected, but different?
Sweet and umami
Binding of sweet tasting molecule to a sweet tasting receptor allows for the activation of PKA, allowing for the phosphorylation of K+ channels and overall depolarization of the cell.
Glutamate binds to umami receptors and the G-beta-gamma will activate phospholipase C. It will breakdown PIP2 into DAG and IP3. IP3 will bind to cation channels to release CA++ into the cell. It will bring sodium into the cell and an overall depolarization of the cell.
How do salty and sour substances become sensed, such that they are converted into signals that reach your brain?
Salty - ions like NaCl
Sour - acidic (H+)
Salty and sour is generally small simple molecules that can cross the cell membrane through ion channels. When it enters, they trigger a depolarization by binding to and activating certain channels.
Sweet, bitter, umami are larger molecules that need to bind to receptors to cause a response.
Explain the pathway which leads to the activation of nuclear receptors. How are hormones able to reach target tissues?
Hormones carried by a serum binding protein is able to move through blood because blood is super hydrophilic and the nuclear receptor binding hormones are hydrophobic. As soon as the receptors bind the hormone and dimerize, these receptors will bind to DNA at specific regulatory regions, typically close to the target genes of those nuclear receptors. The dimerized receptors will recruit co-activators/repressors and will lead to the activation/repression of the gene. This leads to a change in the amount of protein your cell is producing. If the receptors are inhibitory, they will shut off the gene.
What are the three domains that are possessed by nuclear receptors and what is the degree homology between three domains between different families of nuclear receptors?
1) DNA binding domain - share high percentages of homology. This region is responsible for binding of DNA to the backbone.
2) Hormone binding domain - little homology because the ligands are very similar
3) Variable domain - dictates coactivators, corepressors, and other proteins. This region varies between different families of nuclear receptor proteins.
Are DNA binding domains specific to certain sequences of DNA?
It’s very specific. They bind to very short regions of DNA and to multiple parts of the dNA.
What is the typical structure of response elements?
They are either direct or inverted repeats. The nuclear receptors look for specific sequences that have direct/inverted repeats.
Direct: 5’ AGGTCA(N)4AGGTCA 3’
3’ TCCAGT (N)4 TCCAGT 5’
Inverted: 5’ AGGTCA (N)4 TGACCT 3’
3’ TCCAGT (N)3 ACTGGA 5’
Are most activated nuclear receptors bound to individual receptors or dimerized pairs?
Dimerized pairs. One part of the dimer binds to one repeat of the response element of the DNA and the other part of the dimer binds to the other repeat.
What does the ligand binding domain prevent in the event that no hormone is bound to the receptor?
The ligand binding domain prevents the DNA binding domain from interacting with the DNA response element. Once the hormone binds, the receptor will change conformation, open up the DNA binding domain, and allow for the receptor to bind to DNA.
How are nuclear receptors present in the cytosol activated?
They have a chaperone protein that is loosely attached to them. When a hormone binds to the receptor, the inhibitor will dissociate from the nuclear receptor and it will move into the nucleus to dimerize and bind to the response element.
What does the nuclear receptor do as it binds to the DNA? What is the role of the activation domain of these receptors?
It can act as a transcriptional enhancer or repressor. This region is able to increase or decrease transcription of a specific gene through the recruitment of co-activators or co-repressors.
