NERVOUS SYSTEM: SIGNAL TRANSDUCTION Flashcards
How are extracellular signals converted into intracellular events?
signal transduction
define: signal transduction
Signal transduction: the transmission of an extracellular stimulus to an intracellular signal via specific membrane receptors.
Can signal for: altered ion transport, metabolism, gene expression, cell shape or movement, cell growth and division
Describe cell-to-cell communication
- cells release extracellular signaling molecules (e.g. hormones and neurotransmitters) which bind to receptors that are transmembrane, cytosolic or nuclear
- signal is transduced into activation or inactivation or one or more intracellular messengers
- messengers act on targets, including ion channels, transporters, enzymes, cytoskeletal proteins, gene regulatory proteins, cell cycle proteins
- autocrine, paracrine, endocrine
- responses can be fast or slow
Describe the following in regards to ligand-gated ion channels
- What do they open in response to?
- Indirect or direct gating?
- Examples
- What do they allow in?
- structure
- Open in response to binding of small molecules, including hormones, chemicals. Ligand binding opens channel and permits current flow
- Gating can be direct or indirect
- Examples include channels (CNG channels, ATP-gated channels)
- Often non-specific (permeable to Na+ and K+, sometimesCa2+)
- Heteromeric, vary in subunit composition (generally: 5 subunits, each with 4 transmembrane spanning helices)
State the ionotropic receptor for Ach
Ionotropic receptor for Ach is nicotinic Ach receptor
State the metabotropic receptor for Ach
Metabotropic receptor for Ach is muscarinic Ach receptor
What is the result of Ach binding to nicotinic Ach receptor?
Ach binding to nicotinic Ach receptor results in membrane depolarization leading to muscle contraction
What is the result of Ach binding to muscarinic Ach receptor in the cardiac muscle?
membrane hyperpolarization leading to decrease in heart rate
State the ionotropic receptor in the retina
ionotropic glutamate receptor (iGluR)
State the ionotropic receptors involved in synaptic plasticity
AMPA and NMDA glutamate receptors involved in synaptic plasticity
State the metabotropic receptor in the retina
Metabotropic glutamate receptors (mGluR) in the retina and in the CNS
State the metabotropic receptor in the autonomic nervous system
Muscarinic acetylcholine receptors (MAChR) of the autonomic nervous system
How many transmembrane domains make up a metabotropic receptor?
7 transmembrane domains and 1 extracellular ligand domain
Describe the process for GPCR signaling cascades
- Ligand binding to the GPCR leads to activation of the G protein by switching it from a GDP bound (inactive) state to a GTP bound (active state)
- The subunit dissociates from the subunit, both can go on to activate intracellular effector molecules
- Effector activation leads to second messenger molecules (cAMP, Ca2+) that have other cellular effects including (e.g.) opening (or closing) ion channels or regulating gene expression
Describe the structure of g proteins
G proteins are composed of alpha, beta, and gamma subunits
Define: opsin
Opsins are light-activated GPCRs that mediate vision;
What was the first GPCR structure to be solved using x-ray crystallography? It is also the most extensively studied GPCR
Rhodopsin (in rod cells) was the first GPCR structure to be solved using x-ray crystallography and remains the most extensively studied
What are the actions of the second messengers at 3 cellular sites
- Presynaptic neuron: second messengers modulate activity of K+ and Ca2+ channels as well as modulate the transmitter release machinery to regulate its efficacy. This results in change to the size of fast postsynaptic potential mediated by ionotropic receptors
- Postsynaptic neuron: second messengers directly alter the amplitude of postsynaptic potentials by modulating ionotropic receptors
- At the cell body: second messengers affect the function of resting channels and voltage-gated channels in the soma and dendrites. Thus altering a variety of electrical properties of the cell including resting potential, input resistance, length and time constants, threshold, and action potential duration
Describe the activation of G protein
- Ligand binds receptor and activates.
- Receptor interacts with the G protein to promote a conformational change and the exchange of GDP for GTP
- GEFs facilitate the dissociation of GDP and the binding of GTP
- G protein dissociates from the receptor and its a-GTP and By subunits dissociate. Both a-GTP and By can nowinteract with their appropriate effectors (E1, and E2)
- a-catalyzed hydrolysis of GTP to GDP inactivates a subunit and promotes reassembly of the a, b, y trimer
- Members of the RGS family of G protein regulators stimulate GTP hydrolysis with some but not all a subunits
Describe: Gs proteins and Gi proteins
Gs: G proteins that stimulate adenylyl cyclase
- When activated, alpha subunit binds to adenylyl cyclase which activates it and now it converts ATP to cAMP. Increased cAMP upregulates the activity of voltage-gated HCN channels and speeds up heart rate
- cAMP also activates protein kinase A
Gi: G proteins that inhibit adenylyl cyclase
Describe the function of Gt aka transducin
in response to light photoactivating rhodopsin, transducin’s alpha subunit dissociates and activates phosphodiesterase (PDE). phosphodiesterase converts cGMP to GMP. The decreased cGMP levels result in the closing of cGMP- dependent channels that are normally open in the dark. This hyperpolarizes the retina cell and reduces glutamate release
Describe the function of Gq
in response to ACh binding M1 muscarinic receptors in smooth muscle surrounding the bronchi, alpha subunit of the Gq complex dissociates and acts on phospholipase C (PLC). PLC hydrolyzes PIP2 to DAG. DAG activates PKC and IP3. IP3 which acts on IP3 receptors. IP3 receptors open which release Ca2+ from intracellular stores. This results in smooth muscle contraction and bronchoconstriction
Describe amplification via signal transduction
A neurotransmitter can activate many G proteins whose a subunits may activate many adenylyl cyclase which in turn can make many cAMP molecules. This activates many protein kinase A molecules and each kinase can phosphorylate and open many K+ channels
