Signaling #2 Flashcards
What are the major classes of cell-surface receptors?
G Protein-Coupled Receptors (GPCRs), Receptor Tyrosine Kinases (RTKs), Ion Channel Receptors, Nuclear Receptors
The classes of receptors play key roles in cell signaling pathways.
What do second messengers do in signal transduction?
Carry signals from many receptors to elicit cellular responses
Common second messengers include cAMP, Ca++, and inositol phospholipids.
Fill in the blank: The G protein is inactive when bound to _______.
GDP
GTP binding activates the G protein, enabling it to stimulate various signaling responses.
What are GEFs and GAPs in the context of G protein signaling?
GEFs: Guanine nucleotide Exchange Factors; GAPs: GTPase-Activating Proteins
GEFs facilitate the exchange of GDP for GTP, activating the G protein, while GAPs enhance GTP hydrolysis, turning it off.
What is the role of protein kinases in cell signaling?
Transfer phosphate groups to proteins and lipids to regulate cellular activities
Protein kinases are crucial for many signaling pathways and cellular processes.
How do lipid rafts influence receptor localization?
They cluster receptors and signaling proteins to specific regions of the plasma membrane
Lipid rafts are enriched in cholesterol and sphingolipids, providing a platform for signaling.
True or False: Uniform distribution of receptors is common in cell membranes.
False
Receptors typically cluster in specific regions, influencing signaling sensitivity.
What is the function of PDZ domains in receptor clustering?
Recruit and stabilize key synaptic components by binding to integral membrane proteins
PDZ domains are important for organizing signaling complexes at synapses.
What are the basic steps of signal transduction via GPCRs?
- Ligand binding activates the receptor
- Receptor activates a trimeric G protein
- G protein activates an effector enzyme
- Effector generates a second messenger
This process is essential for various signaling pathways in cells.
What is a common effect of cholesterol depletion on lipid rafts?
It disrupts signaling pathways and can induce apoptosis
Cholesterol is vital for maintaining the structural integrity of lipid rafts.
Fill in the blank: The most abundant form of signaling in cells is through _______.
G protein-coupled receptors (GPCRs)
GPCRs are involved in many physiological processes and are targets for a wide range of drugs.
What diseases are associated with GPCR mutations?
- Retinitis pigmentosa
- Hyperfunctioning thyroid adenomas
- Precocious puberty
- X-linked nephrogenic diabetes insipidus
- Short limbed dwarfism
- Hypertension
Mutations in GPCRs can lead to various health conditions, highlighting their importance in cell signaling.
What is the significance of the β2 adrenergic receptor in GPCR studies?
It has a complete three-dimensional atomic structure that aids in understanding GPCR activation
The β2AR is a model for studying GPCR signaling mechanisms.
What are the two basic mechanisms that influence receptor dispersion?
- Lipid rafts
- Scaffolding of membrane proteins
These mechanisms help maintain a high receptor density in specific areas of the cell membrane.
What are the main structural components of GPCRs?
GPCRs are comprised of an extracellular N-terminus, seven transmembrane α-helices, three intracellular loops, three extracellular loops, and an intracellular C-terminus.
The structural theme among GPCRs is palmitoylation of C-terminal tail or intracellular loops.
What is the function of palmitoylation in GPCRs?
Palmitoylation targets the receptor to cholesterol-sphingolipid-rich microdomains that form lipid rafts.
This modification involves the addition of hydrophobic acyl groups to cysteine residues.
What is the shape of the GPCR tertiary structure?
The GPCR tertiary structure is barrel-like, with the seven transmembrane helices forming a cavity within the plasma membrane.
What happens upon ligand binding to a GPCR?
Ligand binding induces a shift in the relative orientations of the transmembrane helices, revealing residues critical to signal transduction.
This process is essential for G-protein coupling.
What role do β-arrestins play in GPCR signaling?
β-arrestins increase the affinity of the intracellular surface for binding, thus turning off GPCR signaling when the C-terminus is phosphorylated.
What are the components of heterotrimeric G proteins?
Heterotrimeric G proteins are assembled from Gα, Gβ, and Gγ subunits.
Fill in the blank: The Gα subunit is bound to _______ prior to activation.
GDP
What occurs when a trimeric G protein binds to an activated receptor?
Dissociation of GDP occurs, leading to binding of GTP to Gα and dissociation of Gα·GTP from Gβγ.
What is the intrinsic function of Gα subunits?
Gα subunits have intrinsic GTPase activity that inactivates Gα·GTP by catalyzing GTP hydrolysis.
List the functions of Gα subunits.
- Gαs: Stimulate adenylyl cyclase
- Gαi: Inhibit adenylyl cyclase
- Gαq: Stimulate phospholipase Cβ
- Gαt: Stimulate cyclic GMP phosphodiesterase
- Gαo: Inhibit adenylyl cyclase
- Gαgust: Stimulate phospholipase Cβ
True or False: All β subunits of G proteins combine with γ subunits to form βγ dimers.
True
What are the functional roles of βγ dimers in G protein signaling?
βγ dimers have a number of control functions in signaling pathways.
What happens when multiple GPCRs bind the same ligand?
Different responses can be generated from the activation of multiple GPCRs by the same ligand.
What is the effect of epinephrine binding to β-adrenergic receptors?
Increases [cAMP], leading to glycogen breakdown in hepatic and adipose cells, increased heart rate, and relaxation of intestinal smooth muscle.
What is the role of α-adrenergic receptors linked to Gi?
Inhibits adenylyl cyclase.
What do α1A-adrenergic receptors linked to Gq stimulate?
Stimulate phospholipase C to generate IP3 and DAG as second messengers.
