Receptors and their signal transduction Flashcards
What are the functions of receptors?
- they need to recognize the mediator
- recognize ligands (molecules that bind to receptors)
- the target cell must revoke a biological response
What is contact dependent intercellular communication?
the cell communication is dependent on contact
→ the cells must make contact in order for cell communication to occurr
What is a paracrine mediator?
molecules that are released from one type of cell and act locally on a different type of target cell
What is synaptic intercellular communication?
neurons trasnsmit electrical signals along their axons and release neurotrasmitters at synapses that affect the function of other neurons or cells that are distant from the neuron cell body
What is endocrine intercellular communication?
hormones that are secreted into the blood and spread in the body
example: hormone
What is autocrine secretion?
release of a molecule that affects the same cell or other cells of the same type
What are the types of intercellular communication?
- gap junctions
- autocrine mediator
- paracrine
- contact dependent communication
- synaptic -endocrine
What are the conditions of a receptor in regards to the ligand bonding?
- the binding of ligand to the receptor has to be reversible
- can be saturated
- the receptor has to be specific, however the specificity is not absolute
What are the two types of intracellular signaling proteins that act as molecular switches?
- signaling by phosphorylation
- signaling by GTP- binding protein
Describe the mechanism of signaling by phosphorylation.
- activated by the addition of a phosphate group
- inactivated by the removal of the phosphate
- The phosphate is added covalently to the signaling protein by a protein kinase
Describe the mechanism of signaling by GTP-binding-proteins.
- activated by the addition of a phosphate group
- inactivated by the removal of the phosphate
- A signaling protein is induced to exchange its bound GDP for GTP
What are the two types of signaling molecules?
- plasma membrane receptors
- intracellular receptors
How do signaling molecules work?
- they directly bind to their cognate receptors located in the plasma membrane
- when ligand is bound they regulate gene transcription
What is another possible means for the path of a signal molecules?
- bind to carrier proteins in blood and diffuse across the plasma membrane
- they bind to cognate so-called nuclear receptors in the cytosol or nucleus
- when ligand is bound, they regulate gene transcription
What is the general mechanism of how cells communicate?
- A ligand binds to a receptor which may be located in the plasma membrane, cytosol, or nucleus.
- This binding activates intracellular signaling proteins
- These proteins interact with and regulate the activity of one or more target proteins to change cellular function.
What do signaling moleculares regulate?
- cell growth
- cell division
- differentiate and influence cellular metabolism
- cytoskeletal-associated events (cell shape, division, migration, and cell to cell matrix adhesion)
How do signal molecules modulate the intercellular ion composition?
they regulate the activity of ion channels and transport proteins
What are examples of plasma membrane receptors?
- G protein-coupled receptors
- Ion channel receptors
- Receptors with enzyme activity
- Enzyme activity-linked receptors
What is the structure of G protein coupled 7TM receptors ?
- 7 transmembrane proteins
- with alpha beta and gamma subunit
How is adenyl cyclase activated?
- stimulatory ligands bind to stimulatory receptors which activates the Gs at the alpha subunit
How is adenyl cyclase inhibited?
inhibited by Gi
What are the effects of Gi/o family proteins?
- inhibition of adenyl cyclase
- inhibition of Ca2+ channels
- activation of K+ channels
- activation of phospholipase A2
Cyclooxygenase is blocked by…?
aspirin
What happens in phototransduction?
- A photon interacts with the receptor and activates the G protein transducer
- The alpha t activates phosphodiesterase (PDE), and hydrolyzes cGMP
→ lowers the intracellular concentrations of cGMP and therefore closes the cGMP-activated channels
What is an example of procaine signaling?
the release of ACh at the neuromuscular junction
What are the two possible functions of ligand gated ion channel receptors?
- excitatory receptor
- inhibitory receptor
What are the ligands of an excitatory receptor?
- Acetylcholine
- Glutamate
- Serotonin (5HT3 receptor)
* specificity Na+/K+*
- Glutamate (but different specificity Na+/K+ and Ca2+)
What are the receptors for the excitatory inhibitor acetylcholine?
nicotinic
What are the receptors for the excitatory inhibitor glutamate and what are they specific for?
- AMPA, Kainate (Na+/K+)
- NMDA receptor (Na+/K+ and Ca2+)
What are the receptors for the excitatory inhibitor Serotonin?
5HT3 receptor
What are the ligands of inhibitory receptors?
- γ-Aminobutyric acid, GABA (type A)
- Glycine
*specificity Cl-*
What is Kd and what does it define?
- Kd is the dissociation constant
- inversely proportional to affinity
- tells us the range that receptor can function
What is the equation of Kd? And what does Kd equal to at 50% binding?
Kd = [R] • [L] / [RL]
Kd= [L]
What does the max tell us?
How many receptors are in the system
What does EC50 tell us?
Defines the potency (inversely proportional)
What is the difference between EC50 and Kd?
Kd is used in regards to binding
EC50 is used in regards to a biological response
What does an agonist do?
evokes a biological response
What’s and antagonist? And what are the two types?
a ligand that does not evoke a biological response
How can we “turn off and turn on” proteins?
- phosphorylation
- GTP binding
What does GEF do?
phosporylatation of GDP which in turn activates the G protein
What does GAP do?
dephosporylatation of GDP which in turn inactives the G protein
What happens when Gs proteins are activate ? And what are they activated by?
- adenyl cyclase is activated
- adenyl cyclase converts ATP → cAMP
-
protein kinase A is activated which phosphorylates target proteins
* Activated by:* beta-adrenergic, ACTH-r
What is the function of phosphodiesterase?
an enzyme that breaks down cAMP → 51 AMP
inhibitor: caffeine
What does the Gi/o protein do in regards to cAMP formation?
inhibits
What are gap junctions?
- allow intracellular signaling molecules to diffuse from cytoplasm of one cell to adjacent cell
- also allow cells to be electrically coupled
