Cell Communication: GPCRs Overview
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Questions and Answers

What is the primary function of GTPase activating proteins (GAPs) in relation to Galpha subunits?

  • To activate second messengers produced by Galpha subunits
  • To stimulate the intrinsic GTPase activity of Galpha subunits (correct)
  • To bind with downstream signaling proteins
  • To inhibit Galpha subunits from hydrolyzing GTP
  • Which role does the Gβγ subunit play in regulating cardiac function?

  • Inhibits the dissociation of Gα and Gβγ
  • Directly hydrolyzes GTP to GDP
  • Stimulates cAMP production to increase heart rate
  • Activates K+ channels to decrease heart rate (correct)
  • What characterizes second messengers in signaling pathways mediated by G-proteins?

  • They act directly on the G-protein subunits
  • They are produced before the first messenger activates the G-proteins
  • They are typically larger proteins that bind to receptors
  • They are synthesized at the membrane and diffuse into the cytosol (correct)
  • Which of the following is NOT a characteristic of the Galpha subunit when bound to GTP?

    <p>It activates downstream signaling proteins directly</p> Signup and view all the answers

    What happens to the Galpha subunit when it transitions from GTP-bound to GDP-bound state?

    <p>It dissociates from Gβγ and inactivates signaling</p> Signup and view all the answers

    What is the primary GTP-binding protein in heterotrimeric G-proteins?

    <p>G-alpha</p> Signup and view all the answers

    In which conformation do G-alpha, G-beta, and G-gamma subunits associate together?

    <p>Inactive conformation</p> Signup and view all the answers

    What triggers GDP release from the G-alpha subunit?

    <p>Binding of a ligand to GPCR</p> Signup and view all the answers

    What happens to the G-alpha subunit upon GTP binding?

    <p>It dissociates from G-beta and G-gamma</p> Signup and view all the answers

    Which subunits of heterotrimeric G-proteins are involved in downstream signaling?

    <p>G-alpha and G-beta-gamma</p> Signup and view all the answers

    Which Galpha subunit is responsible for inhibiting adenylyl cyclase?

    <p>G-alpha-i</p> Signup and view all the answers

    How do G-alpha and G-gamma subunits interact with cellular membranes?

    <p>They are covalently attached to membrane lipids</p> Signup and view all the answers

    What is the effect of GPCR activation on the G-alpha subunit?

    <p>It leads to G-alpha dissociation from G-beta-gamma</p> Signup and view all the answers

    What is the primary role of G-proteins in signal transduction?

    <p>To cycle between active and inactive states depending on bound nucleotides</p> Signup and view all the answers

    Which amino acid residues are primarily targeted for phosphorylation by kinases?

    <p>Serine, threonine, and tyrosine</p> Signup and view all the answers

    What accelerates the hydrolysis of GTP to GDP in G proteins?

    <p>GTPase Activating Proteins (GAPs)</p> Signup and view all the answers

    What effect do GEFs have on G proteins?

    <p>They induce the release of GDP and bind to GTP</p> Signup and view all the answers

    How do the distinct GTP and GDP states influence G proteins?

    <p>They drive allosteric changes that regulate binding properties</p> Signup and view all the answers

    What is the primary function of G-protein coupled receptors (GPCRs)?

    <p>Transmitting signals inside the cell upon ligand binding</p> Signup and view all the answers

    What is a primary function of signal transduction pathways?

    <p>Integrating multiple signals to yield distinct responses</p> Signup and view all the answers

    What is the structural characteristic of GPCRs?

    <p>Seven transmembrane α-helices</p> Signup and view all the answers

    Which statement about feedback regulation in signal transduction pathways is true?

    <p>It regulates an upstream component of the pathway</p> Signup and view all the answers

    Which of the following describes the role of antagonists in relation to GPCRs?

    <p>They prevent agonists from binding and keep the GPCR inactive</p> Signup and view all the answers

    What distinguishes small GTPases from heterotrimeric GTPases?

    <p>Heterotrimeric GTPases contain a specific helical domain</p> Signup and view all the answers

    How do small molecules interact with GPCRs?

    <p>They can act as either agonists or antagonists</p> Signup and view all the answers

    Why are GPCRs significant in pharmacology?

    <p>They are major targets for drug development</p> Signup and view all the answers

    What type of response is initiated by the beta-adrenergic receptor when activated?

    <p>Fight or flight response</p> Signup and view all the answers

    Which of the following statements about GPCR signaling is correct?

    <p>Conformational changes are transmitted to the cytosolic side</p> Signup and view all the answers

    What role does naloxone play in relation to opioid receptors?

    <p>It competes with opioids and keeps the receptor inactive</p> Signup and view all the answers

    What happens if a cell is deprived of survival signals?

    <p>The cell will activate programmed cell death.</p> Signup and view all the answers

    How do different target cells respond to acetylcholine despite having the same receptor type?

    <p>The physiological response varies in different target cells.</p> Signup and view all the answers

    What characterizes fast signaling pathways?

    <p>They alter the activities of existing proteins quickly.</p> Signup and view all the answers

    Which type of signaling occurs when two cells are in direct physical contact?

    <p>Contact-dependent signaling</p> Signup and view all the answers

    Which signaling method communicates over long distances via the bloodstream?

    <p>Endocrine signaling</p> Signup and view all the answers

    What defines autocrine signaling?

    <p>A cell secretes a signal that binds to its own receptors.</p> Signup and view all the answers

    Which signaling mechanism has effects that occur over short distances, typically within a few cell diameters?

    <p>Paracrine signaling</p> Signup and view all the answers

    In which scenario would a signal exert its effect the slowest?

    <p>Changes in gene expression and protein synthesis.</p> Signup and view all the answers

    What does the diverse responses to a single signaling molecule typically depend on?

    <p>The specific receptor type expressed by the target cell.</p> Signup and view all the answers

    Which of the following statements is true regarding signals acting on different time scales?

    <p>Different signals can exert rapid or slow effects based on their mechanisms.</p> Signup and view all the answers

    What is the role of cAMP in cellular signaling?

    <p>It acts as a second messenger to activate protein kinase A (PKA).</p> Signup and view all the answers

    How does caffeine affect cAMP levels in neurons?

    <p>It inhibits phosphodiesterase, thus keeping cAMP around longer.</p> Signup and view all the answers

    What initiates the signaling process that leads to glycogen breakdown in muscles?

    <p>Binding of epinephrine to GPCR.</p> Signup and view all the answers

    What is the outcome of cAMP activation of PKA in gene expression?

    <p>Phosphorylation of transcription factors in the nucleus.</p> Signup and view all the answers

    Which of the following describes the role of phospholipase C (PLC)?

    <p>It cleaves inositol phospholipid to produce diacylglycerol and IP3.</p> Signup and view all the answers

    What does diacylglycerol do in the signaling cascade?

    <p>It recruits protein kinase C (PKC) to the membrane.</p> Signup and view all the answers

    What is the significance of the rise in Ca+2 concentration in cells?

    <p>It regulates gene expression by activating specific transcription factors.</p> Signup and view all the answers

    What is the function of phosphorylase kinase in glycogen metabolism?

    <p>It phosphorylates glycogen phosphorylase to promote glycogen breakdown.</p> Signup and view all the answers

    Which statement is true regarding cAMP signaling pathways?

    <p>cAMP can mediate both fast and slow signaling effects.</p> Signup and view all the answers

    What is the role of inositol 1,4,5-trisphosphate (IP3) in cellular signaling?

    <p>It binds to Ca+2 ion channels in the ER, releasing Ca+2 into the cytosol.</p> Signup and view all the answers

    What types of processes does the rise in cAMP influence?

    <p>Hormone production and long-term memory formation.</p> Signup and view all the answers

    How does the signaling via cAMP and PKA compare to other signaling pathways?

    <p>It is rapid and does not require new gene expression for an immediate effect.</p> Signup and view all the answers

    What is the initial step when GPCR is activated by a ligand?

    <p>It activates heterotrimeric G-proteins.</p> Signup and view all the answers

    What effect does calcium binding to PKC have?

    <p>It activates PKC to phosphorylate downstream targets.</p> Signup and view all the answers

    Study Notes

    Cell Communication 1: GPCRs

    • This lecture investigates cellular signaling, focusing on G-protein Coupled Receptors (GPCRs), their activators, G-proteins, and downstream effectors.
    • Signaling pathways are divided into three components:
      • Cells detect a signal via an appropriate receptor.
      • The signal is relayed within the cell via a series of proteins.
      • The cell responds by changing cellular protein activity, gene expression, or both.
    • Biological signals are diverse, ranging from light, small molecules (e.g., dopamine, morphine), proteins (e.g., Wnt signaling), to mechanical signals.
    • A cell phone analogy for signal transduction: receiving radio signals, converting these into sounds, and vice-versa demonstrates how cells receive signals from various sources and convert them to intracellular responses.
    • Input from the environment (or other cells) elicits specific responses. Cells convert these external signals into intracellular changes.
    • Cells can respond only to signals they can detect.

    Signaling Pathways

    • Eukaryotic cells depend on multiple extracellular signals.
    • Signals can be combined or act alone; this determines cellular responses.
    • Cells only respond to signals they detect and cells can respond differently to the same signal based on cell type and internal factors.
    • Cells use multiple signaling pathways and receptors to generate responses.
    • Cells can respond to signals over varying distances, ranging from direct contact (contact-dependent) to signaling over distances like local signaling (paracrine), or long distance signaling (endocrine).
    • Autocrine signaling is when a cell signals to itself.

    GPCRs

    • GPCRs are the largest family of cell surface receptors in animals (over 700 in humans).
    • GPCRs detect various signals, including odorants, light, and other molecules.
    • GPCRs have a 7 transmembrane helix structure. They have extracellular N-terminus and extracellular loops.
    • Ligand binding to the GPCR's outer surface triggers conformational changes that impact the intracellular components of the receptor allowing for intracellular signaling.
    • GPCRs are major drug targets for many medications.
    • Different GPCRs can be activated by various agonists (molecules that activate the receptors) but also inhibited by antagonists (molecules that bind and prevent activation).

    GTP-Binding Proteins (G-Proteins)

    • G-proteins cycle between active and inactive conformations based on whether they bind GTP or GDP.
    • These proteins are central to intracellular communication.
    • G-proteins exist in active (GTP bound) or inactive (GDP bound) states; they regulate downstream effector activities.
    • G proteins are usually regulated by accessory proteins (e.g. GEFs and GAPs) which promote either the exchange GDP for GTP or stimulate the hydrolysis of GTP to GDP.
    • GPCR activation drives GTP exchange on Galpha.
    • G proteins dissociate into two signaling complexes when activated.

    Signal Transduction Pathways

    • Signal transduction pathways convert a signal from one form to another, allowing the signal to be transmitted and amplified within the cell.
    • Receptors detect input, relay signals to target proteins, and then activate processes within the cell.
    • Pathways can create molecules which amplify signals initiating a variety of possible downstream events within the cell
    • Signals can have rapid/on-off effects (e.g., milliseconds to minutes) or sustained/long-term effects (e.g., minutes to hours), depending on the nature of the signal and pathways/effectors involved.

    Effectors

    • G-proteins can regulate ion channels allowing changes in cell membrane permeability.
    • G-proteins activate membrane-bound enzymes (e.g., adenylyl cyclase and phospholipase C) that make second messengers (e.g., cAMP and IP3).
    • Second messengers trigger downstream actions and effects in the cell to change its state.

    Calcium

    • Low intracellular calcium levels are maintained by calcium pumps on the cell membrane and within organelles like the ER.
    • Calcium signaling is an important intracellular signal controlling multiple cellular processes and is not limited to activating proteins like PKC.

    PKA

    • PKA phosphorylates other proteins, ultimately leading to changes in gene expression; involved in signaling pathways that have both fast and immediate effects and long-term regulatory effects on cell function.
    • PKA is involved in glycogen utilization by the skeletal muscles when activated by cAMP.
    • PKA phosphorylates glycogen phosphorylase, leading to glycogen breakdown and releasing glucose for energy.
    • PKA signaling can also involve changes in long term gene expression.

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    Description

    This quiz explores the fascinating world of cellular signaling through G-protein Coupled Receptors (GPCRs). It covers the components of signaling pathways, types of biological signals, and how cells process and respond to these signals. Gain a deeper understanding of how cellular communication shapes biological responses in various contexts.

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