receptors and signalling Flashcards
what’s a ligand
-any molecule that binds to a receptor, it may be agonist or an antagonist
whats an agonist
-anything that can bind to a receptor to activate a response
what’s an endogenous agonist
-chemical mediators found within the body that bind to a receptor producing a response
-not naturally released by the body
what are the general principles of chemical communication and cell signalling
-chemical mediators= extracellular signal ,molecules e.g. hormones
-these bind to specific receptors on target cells
-this initiates intracellular signals that alter cell behaviour through effector proteins
what’s signal transduction
-process of converting extracellular signal to an intracellular signal or second messenger
what’s convergence
-all cells express multiple types of receptors= single cells can integrate information
-different types of receptors may use similar signal transduction mechanisms which allows for amplification of signalling
-effector system takes in a lot of information from lots of different places
what’s divergence
-most extracellular signal molecules can act on more than one type of cell e.g. the same receptor may be expressed by more than one cell type which allows coordinated response involving multiple organs
-in other words, lots of different receptors from one neurotransmitter
how do receptors recognise and respond specifically to signal molecules
-receptors are macromolecular proteins that serve as recognition sites for NT, hormones e.g. chemicals used in cell-cell communication
-receptors also refer to any protein pf a cell that can bind a molecule, which then modulates some activity of the cell
what are the 3 classes of receptors found on the cel membrane
1) ligand-gated ion channels (ionotropic receptors)
2) G protein-coupled receptors (metabotropic receptors)
3) kinase-linked receptors
-each has transmembrane-spanning segments
-each possesses a ligand binding domain (usually extracellular)
-ligands are hydrophilic so can’t cross the cell membrane
what do receptors within a class share in common
-overall structural features
-they can adopt them slightly depending on the receptor
how many main classes of receptors are there
4 known as ‘superfamilies’
what is the intracellular receptor
-nuclear receptors- either floating in nucleus or cytoplasm
-polypeptides with multiple domains (long strings of AA and really defined)
-ligands are hydrophobic sp are capable of crossing the cell membrane e.g. steroid hormone
-act as transcription factors so can influences and regulates transcription of DNA and RNA
which chemical mediators use which type of receptors
-ionotropic receptors don’t respond to insulin
-small molecule chemical mediators such as AA derived neurotransmitters use ionotropic and metabotropic receptors
-peptide hormones and cytokines use kinds-linked receptors
what does signal transduction and intracellular signals involve
1) ligand binding
2) conformational change in the receptor
3) generation of an intracellular signal o second messenger
-the transductions mechanism and type of intracellular signal influences type, speed and duration of response
what are the cellular effects of receptor activation
-electrical signals e.g. triggering action potentials
-Ca2+ release can lead to contractility therefore muscle movement
-protein phosphorylation leads to changes in enzyme activity
-protein synthesis leads to more channels to be inserted into the cell membrane
how are ligand-gated ion channels opened on agonist binding
-involved in fast synaptic transmission
-endogenous agonists are fast/ classical neurotransmitters stored in synaptic vesicle e.g. ACh, Glutamine (causes excretion) and GABA
-composed of 3-5 subunits e.g. transmembrane proteins
-complex arranged to form a central aqueous pore
-by the agonist binding, Channels open
-channel closes when agonist is removed or receptor entered s ‘desensitised’ state
what does nAChR stand for
-nicotinic acetylcholine receptor
-its an excitatory ligand gated ion channel
what does nAChR do
-is an agonist
-found on skeletal muscle and activated when muscle contracts
-without this, the autonomic nervous system (heartbeat etc ) wouldn’t work
-subunits can be different and not always in the same composition
-an example composition is this: a circle, alpha, gamma, alpha, beta, sigma
-also found in brain as when smoking this is released because smoking contains nicotine
what does opening nAChR’s result in
-excitation
1)activation of ionotropic receptors by excitatory neurotransmitters
2) ions flowing through the open channels
3) changes the ‘excitability’ of cell - membrane depolarisation
-note: NT don’t enter the cel its the ions that do this
how can ligand-gated ion channels cause inhibition
-GABA activates GABAa which causes membrane hyperpolarisation (more -ve) allows chloride into cell
what are G protein coupled receptors
-formed from a single transmembrane protein
-receptor protein spans the membrane 7 times (7transmembrane domains)
-has extracellular binding domains on the outside
-regulates effector proteins via a heterotrimeric GTP-bidning protein (G protein)
-incudes 1 alpha subunit, 1 beta subunit, 1 gamma subunit
-beta and gamma known as beta-gamma because very close
how do heterotrimeric G proteins undergo signal transduction
heterotrimeric G proteins undergo an enzymatic cycle
-bot alpha and beta-gamma subunits can interact with effectors
-alpha subunit changes so GTP can bind instead of GPD
1) in resting state, receptor associates with the inactive G protein heterotrimer
2)upon ligand binding, receptor- G protein complex undergoes conformational change that promotes the exchange of GDP to GTP
3)G protein dissociates from receptor
4) alpha-GTP and beta-gamma subunits dissociate
5)both alpha-GTP and beta-gamma can now interact with their appropriate effectors (E1, E2)
6)alpha-catalysed hydrolysis of GTP to GDP inactivates alpha and promotes reassembly of the trimer
why do different G proteins control the function of different effector proteins
-effectors may be ion channels, or enzymes
-enzymes include adenylyl cyclase and phospholipase C which activates the 2nd messengers which are small diffusible molecules that spread the signal
what does amplification of signalling allow
-amplification of signalling through GPCR regulated 2nd messenger cascades allow signalling amplification and can end up in thousands of different channels
how does Gai and Gas change cAMP and protein kinase A levels
-Gas (stimulatory)
increased adenylyl cyclase
increased cAMP
increased protein kinase A (PKA)
-Gai (inhibitory)
decreased adenylyl cyclase
decreased cAMP
decreased protein kinase A (PKA)
how does Gaq increase intracellular Ca2+ levels through the enzymes phospholipase C
-Gaq activates phospholipase C (PLC) which breaks down PIP2
-this increased IP3 (2nd messenger) (activates receptors on the membrane) and DAG
-this increases [Ca2+]in and increases PKC
what is Gas
-Gs is the type of protein
-alpha is the subunit it mediates
-it activates adenylyl cyclase
what’s Gai
-Gi is the type of protein
-alpha is the subunit it mediates
-inhibits adenylyl cyclase
what’s Gbyi
-Gi is the type of protein
-beta-gamma is the subunit it mediates
-activates K+ channels
what’s Gaq
-Gq is the protein
-alpha is the subunit it mediates
-activates phospholipase C and increases [Ca2+]i
