Signaling #5 Flashcards
What leads to PKA activation in cells?
Generation of cAMP by adenylyl cyclase
cAMP stands for cyclic adenosine monophosphate, a second messenger important in many biological processes.
What role do anchoring proteins play in cellular signaling?
They localize signaling and signaling regulatory elements to specific regions in the cell
Example: PKA and AKAP (A-kinase Anchoring Protein)
What is the function of AKAPs in cardiac muscle?
Assemble multiprotein signaling complexes to create focal points of enzyme activity
They help in the positive and negative feedback control of RYR2 calcium channels.
How do released catalytic subunits of PKA affect target proteins?
They phosphorylate target proteins in the nucleus, such as CREB, regulating gene expression
PKA can also phosphorylate other kinases.
What toxins affect GPCR signaling and how?
Cholera and pertussis toxins
Understanding cholera toxin’s actions is linked to a better understanding of adenomas and uncontrolled growth (acromegaly).
What happens when the beta-gamma subunits of the Gi trimeric G-protein are released?
They can regulate channel activity, such as inward rectifying potassium channels (GIRKs)
This illustrates the modulation of G-protein signaling.
How do photons activate G transducin linked GPCRs?
They activate GPCRs in rod cells, helping us see in dim light
This process involves the conversion of light into electrical signals in the retina.
What is the primary effector protein for many neurotransmitter receptors?
Ion channels
This contrasts with having adenylyl cyclase as the effector protein.
What effect does activation of muscarinic acetylcholine receptors have on cardiac function?
Leads to hyperpolarization of the membrane and decreased heart muscle contraction
This is mediated by the opening of inward rectifying K+ channels (GIRKs).
How does sympathetic release of norepinephrine increase cardiac output?
By binding to β1-adrenergic receptors, generating activated Gαs, elevating cAMP and PKA levels
This reduces the threshold voltage for action potential initiation and increases heart contraction force.
What happens when light hits rhodopsin in photoreceptor cells?
The shape of the pigment changes, activating the GPCR and leading to hyperpolarization of the cell
This process involves the conversion of 11-cis-retinal to all-trans-retinal.
What is optogenetics?
A method using light to control the behavior of cells
The field was named by Dr. Karl Deisseroth in 2006.
What is the significance of cGMP in photoreceptor cells?
It gates Na+/Ca++ channels; its hydrolysis leads to channel closure and hyperpolarization
This prevents the influx of positive ions and stops neurotransmitter release.
Fill in the blank: The first effector activated by Gβγ was the _______.
acetylcholine-regulated inwardly-rectifying K+ channel in atrial myocytes
True or False: Gβγ subunits have a catalytic site.
False
Gβγ acts as a modulator of G protein signaling through regulated protein-protein interactions.
How does cholera toxin affect GPCR signaling?
By preventing GTPase activity, leading to prolonged signaling
This results in continuous activation of adenylyl cyclase.
What is the role of opsins in optogenetics?
Microbial light-activated proteins that convert light into energy
Example: Bacteriorhodopsin (BR).
What physiological response is mediated by GIRKs?
Regulation of electrical excitability in cardiomyocytes and neurons
GIRKs are activated by muscarinic receptors in response to acetylcholine.
What is the significance of the first demonstration of microbial opsin genes?
Achieved optogenetic control of neurons, allowing reliable control of action potentials with light at millisecond precision.
Who were the researchers involved in the first demonstration of microbial opsin genes?
Edward Boyden and Feng Zhang.
What is optogenetics?
A technique that uses light to control neurons that have been genetically modified to express light-sensitive ion channels.
What was the aim of the clinical trial for Retinitis Pigmentosa that started in 2016?
To evaluate the safety and tolerability of GS030 in 18 subjects with Retinitis Pigmentosa.
What does GS030 combine in its treatment approach?
A gene therapy (GS030-DP) with a wearable optronic visual stimulation device (GS030-MD).
What method was used to administer the gene therapy GS030-DP?
Via a single intravitreal injection.
What was the outcome reported by Sahel et al. regarding optogenetic therapy?
Partial recovery of visual function in a blind patient.
In which journal was the study by Sahel et al. published?
Nature Medicine.
True or False: Optogenetics allows for control of neurons without genetic modification.
False.
Fill in the blank: Optogenetics allows reliable control of action potentials with light at _______ precision.
millisecond.
What type of device is GS030-MD?
A wearable optronic visual stimulation device.
What is the primary application of optogenetics mentioned?
Control of neurons.
What was the publication year of the article by Buchen L. on neuroscience?
2010.
What is the focus of the article ‘Neuroscience: Illuminating the brain’?
The advancements in neuroscience related to optogenetics.
