Regulated secretion and toxins Flashcards
What makes regulated secretion different from constitutive secretion?
The vesicles won’t fuse with the plasma membrane and release their contents until they receive a signal to do so
How are vesicles containing neurotransmitters created?
They start out as an empty membrane bubble with the necessary membrane proteins. They use a V-class proton pump to bring in H+ with active transport, then use the energy from that concentration gradient to power bringing in the neurotransmitter with a ligand specific antiporter
What is the signal that triggers the secretion of neurotransmitters?
An action potential
What are the steps for the regulated secretion of neurotransmitters starting with an action potential?
- An action potential causes a change in voltage at the terminal of the pre-synaptic neuron
- A voltage gated calcium channel opens and calcium floods in
- The calcium binds to synaptotagmin and causes it to change shape
- The synaptotagmin releases the complexin and the SNAREs finishing coiling and the neurotransmitters are released into the synaptic gap
What sort of receptors do the neurotransmitters typically bind to on the post-synaptic cell?
GPCRs
How are vesicles “parked” in the active zone until they’re secreted?
They are attached together with synapsin and attached to organized cytoskeletal filaments
How long does it take for synaptic vesicles to be completely cycled?
60 seconds
What are the steps in the cycling of synaptic vesicles?
- Vesicle is filled with the neurotransmitter
- Vesicles move to the active zone
- They get docked at the plasma membrane
- An action potential opens the calcium channels and the vesicles fuse
- The neurotransmitters are imported with an Na+ symporter
- The vesicle gets refilled
What are the v-SNAREs and t-SNAREs used?
v-SNARE is VAMP
t-SNAREs are syntaxin and SNAP-25
What is synaptotagmin?
A protein that is stopping the fusion of the vesicles by keeping complexin in a place that stops the SNAREs from coiling
How does muscle contraction occur?
When the neurotransmitters from a neuron bind to receptors on the post-synaptic muscle cell, it creates an action potential and releases Ca2+ from the ER, which causes contraction
What is injected into the skin with Botox? What is its overall effect?
Botulinum toxin, produced by a bacterium. Causes localized muscle paralysis and reduces wrinkles
What is the cellular mechanism by which botulinum interferes with regulated secretion?
The toxin is made of two chains, the first one binds to neurons and lets the 2nd chain into the cell. That chain is a protease that destroys the VAMP v-SNAREs and prevents the vesicle from fusing. The lack of muscle contraction that results causes paralysis
What is the cellular mechanism by which tetrodotoxin interferes with regulated secretion?
Pufferfish toxin. It inhibits the opening of voltage gated sodium channels, which makes it harder to get an action potential. Without an action potential, calcium levels stay low and the neurotransmitters don’t get released. The muscles can’t contract and get paralyzed
What is the cellular mechanism by which latrotoxin interferes with regulated secretion?
Spider vemon. It pokes holes in the membrane of the neuron and allows the calcium to come flooding in. All the vesicles fuse at the same time and causes contraction all at once then paralysis from no contraction soon after
