Signaling #7 Flashcards
What are GPCRs linked to?
Gq, Phospholipase C (PLC) signaling and PIP2 signaling pathways
What does PKC stand for?
Protein Kinase C
How is PKC activated?
By different domains of PKC being regulated
What regulates ER localized IP3 receptor activity?
Calmodulin
What does calmodulin decode?
Transient rises in [Ca++]
What is the link between NO and calmodulin mediated signaling?
NO activates guanylate cyclase, increasing cGMP which activates PKG, influencing calcium signaling
What is Tubby’s role in signaling?
Tubby is a transcription factor released by activation of phospholipase C
What happens when PIP2 is broken down?
It leads to the release of Tubby, allowing it to regulate gene expression
What is the effect of Tubby mutations in mice?
Mice develop adult onset obesity
What domains does the Tubby protein have?
DNA binding domain and gene transcription activation domain
What does PIP2 facilitate in channel activity?
Rapid modulation of channel activity by localized changes in PIP2 synthesis or breakdown
What is the role of TRPV1 channels?
They are non-selective cation channels that respond to pain-related stimuli
What enhances TRPV1 sensitivity?
Diverse hydrophobic ligands, e.g., capsaicins from peppers
What does Bradykinin do in inflammation?
It activates GPCRs that increase TRPV1 channel activity
What is the effect of Ca++ on calmodulin?
Ca++ binds to calmodulin, partially activating it
What is the role of phosphorylase kinase?
It hydrolyzes glycogen to glucose 1-phosphate
What activates phosphorylase kinase?
Both Ca++ and cAMP
What initiates muscle contraction?
The release of acetylcholine (ACh) at the neuromuscular junction
How many nicotinic acetylcholine receptors are present in muscle?
About 20 million
What is the result of ACh binding to nAChRs?
Allows ~50,000 cations into the muscle cell, causing depolarization
What does the voltage change in muscle cells lead to?
An action potential that spreads over the muscle membrane
What channels interact directly with the ryanodine receptor?
CaV1.1 voltage-operated Ca2+ channels
Where does Ca2+ release occur in muscle cells?
At the triadic junction between the SR and T-tubule
Fill in the blank: The breakdown of PIP2 is linked to the activation of _______.
Tubby the transcription factor
True or False: TRPV1 channels are sensitive to both heat and protons.
True
What type of receptor is RYR1?
The ryanodine receptor (RYR1)
RYR1 is crucial for calcium release in muscle contraction.
Where does the coupling between depolarization and Ca2+ release occur?
At the triadic junction
This is where the sarcoplasmic reticulum (SR) contacts the T-tubule.
What connects the SR and T-tubule membranes?
Aggregates of CaV1.1 L-type channels and RYR1
These aggregates facilitate the transmission of information across the gap.
What triggers the RYR1 to release Ca2+ from the SR?
Voltage-dependent conformational change of CaV1.1 L-type channel
This change occurs in response to depolarization.
What role does Ca2+ play in muscle contraction?
It acts on troponinC to trigger the interaction between actin and myosin
This is essential for muscle contraction.
How is muscle relaxation achieved?
By pumping Ca2+ back into the SR by SERCA1
SERCA1 stands for sarco/endo-plasmic reticulum Ca2+ ATPase 1.
What is the source of energy for muscle contraction?
Glucose stored as glycogen
Glycogen is hydrolyzed to glucose for energy.
What enzyme converts inactive phosphorylase b into active phosphorylase a?
Phosphorylase Kinase
This conversion is crucial for energy supply regulation.
What initiates the control of energy production by adrenaline?
Activation of the cAMP signaling pathway
This pathway is critical in the response to adrenaline.
What receptor does adrenaline bind to?
β-adrenergic receptor
This receptor activates the Gs protein.
What does adenylyl cyclase produce in response to adrenaline?
Cyclic AMP (cAMP)
cAMP acts as a second messenger in signaling pathways.
What is the role of protein kinase A (PKA) in energy metabolism?
It phosphorylates phosphorylase kinase
This activation converts phosphorylase b to phosphorylase a.
True or False: Phosphorylase kinase is sensitive to Ca2+.
True
This sensitivity provides feedback for energy metabolism and contraction.
Fill in the blank: Phosphorylase a hydrolyses glycogen to _______.
glucose
Glucose enters glycolysis to generate ATP for contraction.
