Signal perception – membrane receptors and G-proteins Flashcards
(47 cards)
Why do cells need to perceive their environment
All cells need to perceive their environment to detect
Nutrients
Wastes like toxins etc
Growth factors (hormones etc)
Light
What can be considered the environment of a cell
Anything that is outside of the cell can be considered its “environment”
Molecules in solution
Other cells are included in this as cells need to communicate with each other during processes such as the human immune response
Cells which are joined together are also part of each other’s environment – occurs in tissues or organs as alternately differentiated cells are joined together to perform a specific function
What are the properties of receptors
Must have a ligand specificity (only respond to a certain signalling molecule)
Receptors can be cell or tissue specific too
Binding affinity of a receptor needs to be such that it is able to detect the ligand at concentrations within the vicinity of the cell
The receptor must be able to transmit the signal into the cell and initiate a singal transduction cascade
What are the types of receptors
G protein-linked (GTPase protein linked)
Ion channel-linked
Receptors with intrinsic enzymatic activity
Receptors linked to tyrosine kinases
Intracellular receptors (some extracellular signals such as steroid hormones can pass through the cell membrane due to being lipid soluble
Where are ion channel receptors found mainly
Frequently found in the post synaptic membrane for neurotransmission
What happens to ion channel receptors when a ligand binds
Binding of the ligand alters the membrane permeability to ions – caused by a conformational change
How do ion channel receptors usually exist
Generally exists as a protein complex – α,α’,β,γ,δ subunit
5 separate homologous polypeptides encoded for by 4 differnet genes – forms a ring structure (hydrophilic channel)
How is the diversity of ion channel receptors high
Alternative splicing of the receptor subunits plus different combinations of subunits allow for tissue specific receptors increasing the diversity
How do these receptors work during neurotransmission
Electrical signal arrives at the pre-synaptic body
Acetylcholine is released into the synaptic cleft
Acetylcholine binds with it’s cognate ion channel- linked receptor on post-synaptic membrane
→ Conformational change (channel opens)
What are receptors with intrinsic enzymatic activity
These are a heterogeneous class of receptor, which are characterised
by the presence of a cytoplasmic catalytic domain within the
polypeptide
What is an archetypal example of this type of receptor
Receptor tyrosine kinases (RTKs)
How is the catalytic activity mediated
Catalytic activity may be guanylyl
cyclase, phosphatase or kinase
How is the catalytic activity regulated
Extracellular ligand binding
What is the key difference with receptors that have separate enzyme activity
Several receptors do not contain tyrosine kinase activity so must recruit them upon ligand binding
What happens upon IFNγ binding
Binding to IFNγ to ligand binding domain initiates receptor dimerisation and Janus kinase (JAK) activation
What else is also activated upon IFNγ binding
Also activates regulatory proteins – STATS (signal transducer and activator of transcription) - dock
What do G protein-linked receptors activate
This activates a G protein (GTPase protein – has enzymatic activity)
How many different hormone ligands activate G protein coupled receptors (name 5)
Acetylcholine
Glucagon
Oxytocin
Prostaglandins
Thyrotropin
Dopamine
Histamine
Vasopressin
Serotonin
Parathyroid hormone
Adrenalin
Leukotrienes
Thrombin
Why are g protein coupled receptors of therapeutic interest
they are key regulators of numerous physiological processes and are implicated in many diseases
What does ligand binding to G protein-coupelled receptors cause
Ligand binding causes a conformational change in the receptor which activates the G protein
How can the binding be altered
These can also be altered by phosphorylation – PKA (cAMP dependent protein kinase) can phosphorylate these receptors multiple times
What does PKA do if it phosphorylates a GPCR
Deactivates the receptor directly or expose a β-arrestin binding site
What is the structure of a heterotrimeric G protein
Made of 3 non-identical peptide subunits - αβγ
What does a conformational change from ligand binding induce in a heterotrimeric G protein
this allows the guanidine nucleotide exchange factor (GEF) access – GTP/GDP exchange
