Desensitization and Sensory System

Question 1

True or False

____Most characterized signaling pathways act through protein kinase (PK) activation

In humans, ~520 PK genes total, >400 Ser/Thr and 90 Tyr kinase genes

In humans, Serine (86%), Theroine (12%), and Tyrosine (2%)

___Fewer signaling pathways act through protein phosphatase (PP) activation

There are fewer PP~160 genes, of which ~100 protein tyrosine phosphatase genes

PP is critical to the dynamic reversibility of the phosphorylation cycle, and some are regulated

Answer 1

True

Question 2

Fill in the blanks for the Evolution of Phosphorylation sites

___________________- provides a mechanims for the rapid, reversible control of protein function.

Fundamentally, adds a negative charge to __________ side chains, sometimes mimic the phosphorylated state of a protein.

Relevant __________ are presnet in ____________ with conserved basic social rediuses

The evolution of phosphorylation sites from ________ and _________ procides a rationale for why phosproylation sometimes actiates proteins and help explain the origins of this important comlex process.

Answer 2

Protein phosphorylation

amino acid

acidic residue; salt bridges

glutamate; aspartate

Question 3

Which activation mechanism is involved in calmodulin binding to an inhibitory regulatory site that triggers a local conformation change, that is allosterically coupled, to the displacement of an autoinhibitory peptide from the active site?

Answer 3

Calcineurin activation

Question 4

Calcineuirn dephospirylation of __________ transcirption factor is crucial to lymphocyte (epsically T cells) actication

Answer 4

NFAT

Question 5

What is Desensitization?

Answer 5

The channel stays in place, does not pass ions. It only happens at receptors

Question 6

Looking at the image how can a GPCR desensitize?

Answer 6

1. Ligand binding leads to a conformational change in cytoplasmic domains of receptor, enhances binding to G proteins but also make the receptor in a preferred substrate
2. Ligand bound GPCR activates GPCr kinases or GRK which are pre-bound to the GPCR complex.
3. Phosphorylation of GPCR occurs primarily on Ser residues in the S5-S6 loop and C-terminus, which leads to binding of arrestin.

Desenitztated the GPCR

Question 7

What are the three effects of arrestin binding to GPCR (Destination)?

Answer 7

Receptor inactivation

Blocks interaction with heterotrimeric G proteins.

Receptors still on the cell surface and can bind ligand, but cannot activate via G Proteins. Reversible via dephosphorylation

Receptor Sequestration

Serves as a signal for internalization

The receptor cannot bind extracellular ligand as it, not on the cell surface. Reversible via dephosoprylation. (The end of endocytosis)

Receptor downregulation

Targets GPCRs to the lysosome for degradation

Receptor no longer exists in the cell, need to synthesis new receptor to regain responsiveness

Question 8

What is the difference between Homologous and Heterologous GPCR Desnsnitization?

Answer 8

Homologous GPCR Desensitization

Only the signaling pathways specific for stimulating ligand is affected, acts via a GRK bound to the GPCR.

Specific feedback to overactive GPCR type, other GPCRs unaffected and can continue to signal.

Heterologous GPCR Desensitization

Multiple GPCRs are affected, through the activation of protein kinases that are the downstream target of many different signaling pathways

General feedback to an entire signaling system,

typically occurs in response to a higher and longer stimulus.

Question 9

______ a.k.a. _______ system contain ________ sensory neurons expressing only a single odorant receptor.

The human genome has 500-700 odorant receptor genes, although over half may be pseudogenes.

Answer 9

Smell

Olfactory (2)

Question 10

True or False for the following statements related to the olfactory sensory system

_____ Sensory System uses Gs alpha sensory.

______ Increased cAMP levels lead to cAMP binding to and opening of cAMP-gated ion channel, which binds intracellular. This leads to depolarization of olfactory neurons and increased excitatory synaptic transmission to olfactory bulb target neurons

Answer 10

False, Sensory Systems uses G(olf) a Heterotrimeric protein.

True

Question 11

What is the Key to Photoreception in the Vision System?

Answer 11

CGMP Degreattion by Signal-Activated Phosopodiesterase is Key to Photoreception

Question 12

True or False for this Vision System statement

_____ Decreased cGMP levels and closing of cGMP-gated channels lead to acute hyperpolarization of photoreceptors and inhibition of tonic excitatory synaptic transmission by target bipolar cells.

____ Activation of Photoreceptor leads to decreases in Excitatory Transmission. At rest the channel is active

Answer 12

Both are true

Question 13

Looking at this image that pertains to information about photoreceptors (vision).

Please label correctly the stoichiometric and catalytic steps.

Answer 13

All red errors are displaying catalytic steps

All black arrows display the Stocihometric steps

Question 14

Choose the correct options

>100 different mutations in the rhodopsin (GPCR) gene, responsible for (5%/ 15%/ 25%) of all types of congenital retinal degeneration, generally dominant

(~100/150) mutations have been reported to date in the opsin (GPCR) gene

mutations in PDR subunits: ___________

________: muations in opsin genes (the cone GPCRs, as opposed to rodopin in rods), 2 of 3 opsin genes on X chromsomse, in 5% of males, <1% of female. Red-green is most common form

_______________: autosomal recessive congential ocular disorder characterized by total color blindess, low visual acuity, ohotopbia, and nstagmus. Mutations in cone-specific cycclic nelcotide gated (CNG) channels CNGA3 and CNB3 or conc-specific transdusin GNAT2

Answer 14

15%

~150

autosomal recessive forms

Color blindness

Achromatopsia