Lecture 20- Receptors Flashcards
What do polyribosomes do?
Translate mRNA free in cytosol
What is the post synaptic density?
An electron dense area, packed with proteins
What is ATP like?
Nucleotides can act as extracellular
signalling molecules
* ATP can act as a neurotransmitter
* Remember its really important role in energy
metabolism, and a source of phosphate groups
* ATP is co-stored and co-released with
classical neurotransmitters
* ATP acts on purinergic receptors
* both ion channel and G-protein coupled
Do all vesicles have only one type of receptor?
No some vesicles have mixed categories
What is an example of an enzyme linked receptor? How does it work?
Receptor tyrosine kinases”
* Cytosolic domain with intrinsic enzyme (enzyme part of receptor)
activity
or
* Direct association with an enzyme (enzyme close by)
- Note: each subunit of an enzyme-linked receptor usually has only one
transmembrane domain.
For receptor tyrosine kinases is the kinase part of the receptor?
No, but it is an important part of the complex
What is brain derived neurotrophic factor an example of? How does it work? What is it’s function?
-An enzyme-linked receptor
How does it work:
-Neurotrophins bind to TrkB receptors (which are dimers which have a neurotrophic binding site externally and an intrinsic tyrosine kinase domain inwardly)
Function:
-Brain derived neurotropic factor (BDNF) is a neurotrophin
-Neurotrophins are proteins required for the development of the nervous system
-BDNF was first identified as a survival promoting protein and is a member of the
neurotrophin family of growth factors
-High levels of BDNF are found in the hippocampus
-BDNF plays an important role in neuronal
plasticity
How is BDNF synthesized and packaged/ released?
- Synthesized as the precursor proBDNF
- ProBDNF is not an inactive precursor, it is a signalling protein in its own right
- Both are released in an activity dependent
manner
-BDNF is is packaged into dense core vesicles
What is BDNF associated with?
BDNF expression is associated with
* normal and pathological aging
* psychiatric disease
What lifestyle choice enhances the expression of BDNF
- Exercise enhances the expression of
BDNF in normal and pathological
conditions.
How do the constituted and regulated pathways of BDNF release from vesicles have opposing functions?
Regulated pathway:
-Increased mature BDNF
causes…
-Pro survival effects
-Facilitates LTP
Constitutive pathway:
-Increase in pro BDNF
causes…
-Pro-apoptotic effects
-Facilitates LTD
Pro and mature forms of BDNF have opposite effects
At the ionic /cellular level how does BDNF/ TrkB work?
- BDNF undergoes Ca2+ influx-dependent
release from pre and postsynaptic sites - act on ligand-gated ion channels
- voltage-gated ion channels
- second-messenger pathways
- which mediate fast and slow synaptic transmission in neurons
This has multiple actions in the cell
What does it mean when we say Brain derived neurotropic factor (BDNF)
Alters “local protein synthesis” and gene expression….
-Change last for long time
-Regulate the transmission of MRNA and synapses
What is Endocannabinoids an example of? What are they and what do they do?
-It’s a presynaptic target
- Anandamide and arachidon-oylglycerol (2-AG)
-Endogenous ligand for the cannabis receptors (CB1 and CB2)
-small lipid soluble molecules
-synthesized in postsynaptic terminals in response to Ca2+ influx
-acts as a retrograde signal to the presynaptic terminal
-activates CB1 receptors which are coupled to G-proteins
-There are more CB1 receptors than any other
G-protein-coupled receptor in the brain
What does medical marijuana do? What is it an example of?
-“medical marijuana” to stimulate appetite in
patients with chronic diseases, cancer and
AIDS, via enhancing the sense of smell
-Is a Endocannabinoid
What are some fast acting receptors?
Ligand-gated ion channels
* milliseconds
* have intrinsic ion channels (ligand gated
ion channels)
* channel opens to allow influx or efflux of
ions
* excitatory or inhibitory depending on ion
involved and its direction of movement
What are some examples of neurotransmitter that act on ligand gated/ fast acting receptors?
Glutamate and GABA
most CNS synapses are mediated by the
amino acids:
* glutamate (Glu),
* gamma-aminobutyric acid (GABA), or
* glycine (Gly)
What does GABA stand for and what are the two types of receptors that it can act on? (what are these receptors types)
GABA: Gamma aminobutyric acid
GABA-A receptors: ionotropic
GABA-B receptors: metabotropic
How is GABA synthesized? What does this mean in terms of localizing GABA?
- GABA is an amino acid but it is not found in proteins
- GABA is synthesized in GABA’ergic neurons by glutamic acid decarboxylases
(GADs). - GADs therefore are good markers for GABA’ergic neurons
What cycle exists with GABA?
-Synthesized in the GABAergic neuron (presynaptic terminal). Goes from glutamine to glutamate then GABA
-GABA then loaded into vesicles via a neurotransmitter
-Goes across clef interacts with receptors on post synaptic neuron
-Then taken up by astrocytes for metabolism
-Glutamine is returned to the presynaptic terminal via the astrocyte so the process can repeat (recycling mechanism)
Where are GABA-A receptors located?
- Widespread- CNS and PNS, e.g.
- Limbic system
- Eye
- Amygdala
- Neurons, oligodendrocytes and
Schwann cells - NMJ
Are GABA-A receptors diverse?
Yes, there is a huge variety of subunits that can make them up
What is the structure of GABA receptors like?
-Each segment= a subunit
-Between subunits are GABA binding sites which are not specific to the subunit
-Across the membrane there is an Extracellular end terminal, 4 transmembrane domains and intracellular end terminal
What type of electrical potential are GABA-A receptors associated with? What happens?
Inhibitory Postsynaptic Potential (IPSP)
* Activation of GABA (or glycine)-gated ion
channels causes an IPSP.
* An inhibitory postsynaptic potential (IPSP) is a
transient hyperpolarization of the postsynaptic
membrane potential caused by the presynaptic
release.
* Via opening of Chloride ion channels and resulting influx of Cl-
* Results in inhibition of the target cells
* More negative inside, and thus less likely to fire
* GABA’ergic interneurons
* Modulatory effects within a network
