Adrenergic Receptor Signalling: L14 & L15

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Questions and Answers

What is a key function of a cell-type-specific signalsome during differentiation?

To express a unique set of signalling components (correct)

To eliminate all other signalling pathways

To prevent any form of cellular communication

To produce energy for cellular activities

What consequence can arise from abnormal remodelling of cellular signalsomes?

Improved cellular communication efficiency

Development of signalling defects linked to diseases (correct)

Increased cellular energy production

Enhanced immune response

Which aspect of adrenergic activation is highlighted in relation to tissue response during the flight or fight response?

It exclusively activates alpha adrenergic receptors.

It universally induces the same physiological effect across all tissues.

It creates a unique signature for each tissue's response. (correct)

It only affects non-vascular tissues.

How do beta adrenergic agonists influence myocardial contraction?

By increasing the affinity of calcium to contractile proteins Signup and view all the answers

Which of the following statements best compares alpha and beta adrenergic receptor signalling pathways?

Alpha receptors primarily decrease cell response, while beta receptors increase it. Signup and view all the answers

What effect does cAMP have on glycogen synthase?

Decreases its activity Signup and view all the answers

Which component of the signal transduction pathway is responsible for switching off the signal?

GTPase activity Signup and view all the answers

What effect does b2-adrenergic stimulation have on glycogen in the liver?

It induces glycogenolysis. Signup and view all the answers

What is the role of phosphodiesterase (PDE) in cAMP signaling?

Hydrolyze cAMP Signup and view all the answers

How does a2 receptor signaling affect insulin secretion in pancreatic beta-cells?

Attenuates glucose-induced insulin secretion. Signup and view all the answers

What is the role of bg subunits released from Gi/o activation?

They induce specific signaling pathways. Signup and view all the answers

The b-adrenergic receptor kinase plays a role in which aspect of GPCR signaling?

Phosphorylating GPCRs Signup and view all the answers

Which receptor signals through incorporation of GIRK channels?

a2-adrenergic receptor Signup and view all the answers

What is the primary effect of increased cAMP levels in a cell?

Increase glycogen breakdown Signup and view all the answers

What physiological change occurs during hyperpolarization?

Making the membrane potential more negative. Signup and view all the answers

What role does b-arrestin play in GPCR signaling?

It desensitizes the GPCR Signup and view all the answers

What is the primary ion involved in GIRK channel signaling that leads to hyperpolarization?

Potassium ions (K+) Signup and view all the answers

Which process does increased cAMP promote in the liver?

Gluconeogenesis Signup and view all the answers

What happens when the GPCR's c-terminal tail is phosphorylated?

It recruits b-arrestin Signup and view all the answers

Which pathway is inhibited by pertussis toxin according to a2 receptor signaling?

Inwardly rectifying K+ channel pathways. Signup and view all the answers

Which substrate protein is directly phosphorylated by PKA?

Glycogen phosphorylase Signup and view all the answers

What effect does adrenaline have on adipose tissue through b3 and a2 receptors?

It enhances cAMP synthesis and lipolysis. Signup and view all the answers

What is the function of an adaptor protein in a signal transduction pathway?

Facilitate protein interactions Signup and view all the answers

What role does a ligand-bound GPCR play in the PLC signaling pathway?

Acts as a GEF for Gaq Signup and view all the answers

Which of the following statements about the PH domain in PLC is correct?

It interacts with phosphoinositides. Signup and view all the answers

What is the primary function of DAG in the phosphoinositide PLC pathway?

To serve as a second messenger Signup and view all the answers

Which domain in the PLC enzyme is primarily involved in enzyme activation?

TIM barrel Signup and view all the answers

How does Gaq become activated in the PLC pathway?

Upon GDP to GTP exchange Signup and view all the answers

What is the role of the C2 domain in the PLC family of enzymes?

To bind calcium and the membrane surface Signup and view all the answers

Which ligand is most closely associated with activating the a1-adrenergic receptor?

Epinephrine Signup and view all the answers

What outcome is associated with the activation of the PLC pathway in smooth muscle cells?

Increased contraction Signup and view all the answers

What occurs first in the activation cycle of heterotrimeric G-proteins?

Conformational change in the receptor Signup and view all the answers

What effect does GTP exchange have on the Ga subunit of the G-protein?

It stimulates the disassociation from the bg subunits Signup and view all the answers

What is the role of cAMP in the signaling pathway described?

It dissociates from the R-subunits of protein kinase A Signup and view all the answers

What component does the inactive form of protein kinase A consist of?

Two regulatory and two catalytic subunits Signup and view all the answers

What is the final step in the activation cycle of the Ga subunit?

Stimulation of GTPase activity Signup and view all the answers

What is the significance of the lipid modification mentioned in the context of the G-protein cycle?

It inserts the subunits into the membrane Signup and view all the answers

Which of the following best describes the function of adenylate cyclase in this signaling pathway?

It converts ATP to cAMP Signup and view all the answers

What was a notable achievement of Edwin G. Krebs related to protein kinase A?

He shared the Nobel Prize in 1992 for his research Signup and view all the answers

What structural change occurs with the conversion of phosphorylase b to phosphorylase a?

Formation of α helices Signup and view all the answers

In muscle tissue, which molecule acts as a potent activator of phosphorylase in the absence of phosphorylation?

AMP Signup and view all the answers

What is the role of phosphorylation at Serine 14 in phosphorylase?

Induces a conformational change far from the active site Signup and view all the answers

How does phosphorylation affect phosphorylase's active site?

It alters the conformation of the active site Signup and view all the answers

What is required for phosphorylase to be active in the liver?

Phosphorylation Signup and view all the answers

What cellular response does cAMP activation of PKA coordinate?

Increased glucose synthesis and release Signup and view all the answers

Which statement is true about phosphorylase b?

It is the inactive form of phosphorylase Signup and view all the answers

What type of secondary structure is primarily involved in the active form of phosphorylase?

α helices Signup and view all the answers

Study Notes

Cell Signaling Cascades and Responses

Each cell type possesses a unique collection of signaling components, a "signalsome."
Cell differentiation leads to the expression of a specific set of signaling components. These specialized "signalsomes" govern the cell's specific functions.
Alterations in cellular signalosome remodeling can result in signaling defects impacting normal cellular functions.

Signal Transduction by G Proteins

The expansion of G protein signal transduction over the past 15 years has seen an increase from 3 to 16 α subunits and βγ dimers.
Receptor Tyrosine Kinases play a role in cell signaling.

β-adrenergic Agonists and Myocardial Contraction

β-adrenergic agonists significantly enhance myocardial contraction.
These agonists induce varied responses in different tissues.

Alpha and Beta Adrenergic Receptor Signaling Pathways

Alpha and beta adrenergic receptors have distinct signaling pathways, leading to different cellular responses.

Protein Phosphorylation and Downstream Signaling

Protein phosphorylation acts as a critical regulator of downstream signaling pathways.

Adrenergic Activation and Fight-or-Flight Response

Adrenergic activation triggers diverse responses in various tissues during the fight-or-flight response. This includes increased heart rate, strength, and energy supply to muscles. Other responses occur simultaneously, like decreased blood flow to the stomach and intestines.
Adrenaline and noradrenaline (epinephrine) are crucial in this response.

Adrenergic System

Post-ganglionic fibers within the autonomic nervous system release norepinephrine at target locations.
The adrenal medulla releases adrenaline into the bloodstream as part of the fight or flight response.
Specific cell types (neural crest cells and secretary cells in the medulla) comprise the adrenal medulla.

Alpha and Beta Adrenergic Receptor Pathways

Different cellular responses arise from distinct receptor pathways for alpha and beta adrenergic signals.

Signal Transduction Pathway

Signaling cascades involve a sequence of molecular interactions within a cell, initiated by an extracellular signal.
Extracellular signals (hormones, cytokines, growth factors) bind to receptors on the cell surface or inside the cell.
This triggers intracellular signaling molecules. Adaptor proteins help these molecules switch between "on" and "off" signaling states.
This cascade culminates in a cellular response (e.g., gene expression, enzyme activation).

Glycogen Breakdown (Liver)

Adrenaline initiates glycogen breakdown within liver cells.
The process involves an enzyme (phosphorylase) converting glycogen to glucose. The process utilizes water.
Two forms of phosphorylase (phosphorylated and non-phosphorylated) have been identified and characterized.

Membrane Pellets and Adrenaline

Adrenaline acts on membrane components to initiate events that ultimately activate phosphorylase.
These membrane events ultimately result in a water-soluble product triggering phosphorylase activation.

cAMP as a Second Messenger

cAMP is a second messenger critical for eliciting the cellular response to adrenaline.
Adenylate cyclase catalyzes its formation, increasing the level of cAMP within the cell when stimulated by adrenaline.

Adenylate Cyclase

The enzyme adenylate cyclase is membrane-bound and involved in generating cAMP, a crucial step in the response to adrenaline.
Different isoforms of adenylate cyclase exist and are regulated by Ga-GTP and Ca2+/calmodulin. This regulation enables tissue-specific responses.

G-protein Activation and cAMP Synthesis

G protein activation by hormones (ligands) leads to increased cAMP production.
G-proteins (heterotrimeric) are crucial to this activation by causing GDP to exchange for GTP, triggering subsequent dissociation steps.

G Protein-coupled Receptor Signaling

GPCR (G-protein coupled receptor) activation initiates intracellular signaling pathways involving cAMP.
The hormone/ligand binding to the receptor initiates the downstream cascade.
The cascade of events ultimately leads to cAMP production and activates protein kinase A.

Protein Kinase A Activation (PKA)

cAMP activates protein kinase A (PKA).
This leads to the dissociation from its inhibitory/regulatory subunit(s).

Phosphorylase Kinase

Phosphorylase kinase activity is a direct downstream target of cAMP-dependent protein kinase (PKA).
Phosphorylase kinase plays a role in glycogenolysis, regulating glycogen breakdown in response to extracellular signals, converting phosphorylase b to phosphorylase a to achieve this.

Phosphorylase Activation and Glycogenolysis

Phosphorylase is activated to initiate glycogenolysis (glycogen breakdown to glucose).
Phosphorylation is crucial in regulating phosphorylase activity, controlling cellular responses to extracellular signals.

Phosphorylase Regulation

Glycogen phosphorylase activity can be regulated allosterically (by AMP) or through phosphorylation.
Regulation occurs via AMP binding and phosphorylation of Ser14 to activate the enzyme. This affects its activity.

Phosphorylation-mediated Conformation Changes

Phosphorylation of phosphorylase induces a conformational change in the active site, increasing its activity.
This results in a physical change that increases the enzyme activity.

cAMP-Dependent Output Pathways

cAMP activates multiple downstream pathways in various cells coordinating responses in response to adrenaline.
These coordinated outcomes direct cells to utilize energy and glycogen stores as required during specific stimuli such as the fight or flight response.

Receptor Desensitization

Mechanisms exist to terminate or modulate GPCR and cAMP signaling, including receptor desensitization, involving the phosphorylation of receptor tails.

Phosphoinositides as Messengers

Phosphoinositides are a group of lipids that act as important signaling molecules, affecting diverse cellular processes.

Phospholipase C Activity

Phospholipase C enzymes hydrolyze phosphoinositides, leading to the formation of intracellular signaling molecules (DAG and IP3).
Different PLC isoforms respond to varying stimuli and induce downstream effects.

Protein Kinase C

DAG and Ca2+ activate Protein Kinase C (PKC) which is a key downstream target in many intracellular signaling pathways.
These proteins can be utilized to regulate various cellular processes.

Cellular Responses to Adrenergic Stimulation

Different cells exhibit different responses to adrenergic stimulation due to the diversity of signaling pathways activated (e.g. alpha and beta isoforms) that result in different outputs.

G-protein and PKA Signaling Coordination

G-protein coupled signaling can coordinate multiple downstream effects, influencing multiple cellular processes.

Diverse Inputs, Shared Cascades

Cells can respond to many different stimuli, but often utilize shared transduction pathways (e.g., using cAMP signaling to control several crucial cellular processes).
The same receptor, in different cell types, can elicit divergent cellular outputs (e.g. glycogenolysis versus lipolysis).

Additional Notes

The provided text contains information about specific signaling pathways, including details about the effects of adrenaline (epinephrine) and noradrenaline, affecting diverse responses within various tissues.
Signaling pathways for cell processes like cardiac function and glycogen breakdown are comprehensively explained.

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Description

This quiz explores the intricate signaling mechanisms involved in adrenergic receptors during cellular differentiation and tissue response in stress situations. Participants will answer questions related to the functions of signalsomes, cAMP signaling, and the effects of specific adrenergic agonists on myocardial contraction and glycogen metabolism.