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Why do cells need to communicate?
To respond individually and as part of a tissue to internal and external signals, including those from the environment and other parts of the body.
What type of signals are most commonly used in cell communication?
Chemical signals, such as hormones.
What are the two major types of secreted signaling based on distance?
Local signaling (paracrine, synaptic) and long-distance signaling (endocrine).
What are the types of local signaling?
Paracrine signaling: nearby target cells respond
Synaptic signaling: neurotransmitters act on adjacent cells
What is paracrine signaling?
Paracrine signaling is any type of signaling where signals bind to receptors and stimulate adjacent cells.
Define paracrine signaling and give an example.
Signaling molecules act on nearby target cells.
E.g., Fibroblast Growth Factor (FGF) during blood clotting.
Define synaptic signaling and give an example.
A type of paracrine signaling involved in communication between neurons.
Occurs between neurons at synapses.
Neurotransmitters are released from a neuron’s axon terminal into a synapse, binding to receptors on a target cell (e.g., muscle or neuron).
Example: Acetylcholine (ACh).
Where are neurotransmitters stored before release?
In vesicles at the end of axon terminals.
What happens when neurotransmitters are released into the synaptic space?
They bind to receptors on the target cell and induce a change.
What kind of change do neurotransmitters usually induce in the target cell?
Opening of channels that let ions in.
Name a neurotransmitter used in synaptic signaling.
Acetylcholine (ACh).
What kind of target cell responds to acetylcholine?
Muscle cells (among others like neurons).
What is an example of long-distance signaling?
Insulin released by pancreatic beta cells travels through the bloodstream to distant target cells.
What type of signaling involves hormones acting from a distance?
Long-distance signaling.
How do hormones travel to their target cells in long-distance signaling?
Via the circulatory system.
What cells secrete insulin?
Pancreatic beta cells.
How does insulin reach its target cells?
It enters the bloodstream and travels to various cells in the body.
What are the 3 steps of cell signaling?
Reception: ligand binds to receptor
Transduction: receptor activates intracellular proteins
Response: cellular functions are triggered
What is a receptor and what does it do?
A specialized membrane-bound protein that detects a ligand and triggers an internal response.
What binds to a receptor during reception?
A ligand or signaling molecule (also called primary messenger).
What types of molecules can act as ligands?
Hormones, neurotransmitters, growth factors.
What change occurs in the receptor upon ligand binding?
A shape and/or chemical change.
What occurs during the reception stage?
A ligand binds to a receptor, causing a shape (conformational) change in the receptor.
What is transduction in signaling?
A series of intracellular changes and protein activations—often a phosphorylation cascade—triggered by the activated receptor (altered protein activates another protein).
Q: What happens during transduction?
A: The activated receptor activates another protein, starting a relay of changes.
What are relay molecules in transduction commonly called?
Second messengers.
What is a common mechanism in the signaling cascade during transduction?
Phosphorylation cascade
What structural change happens to the receptor to begin transduction?
A conformational (shape) change.
What does the conformational change allow?
Interaction with intracellular signaling proteins.
How is the signal amplified during transduction?
Multiple proteins are sequentially activated in a cascade.
What is the cellular response phase?
Activated proteins cause specific cellular activities (e.g., gene expression, metabolism, movement).
What occurs during the response stage of signaling?
The cell performs one or more specific functions based on activated proteins.
What determines which ligand can bind a receptor?
Shape (structure determines function); it's like a lock and key.
Where are most receptors located?
On the outside of transmembrane proteins.
What is the role of the transmembrane protein in signaling?
It has a binding site for a ligand and transmits changes internally.
What is a transport channel protein’s role in signaling?
Binding of a ligand changes its shape, causing an internal effect without transport
Are receptors for lipid-soluble molecules membrane-bound?
No, they are not.
Where are receptors for lipid-soluble molecules located?
Inside the cell (cytoplasm/nucleus) because lipid-soluble ligands can pass through the membrane.
Do lipid-soluble molecules need a receptor to enter the cell?
No, they can diffuse through the lipid bilayer.
Give an example of a lipid-soluble signaling molecule.
Steroid hormones.
Once inside the cell, what do lipid-soluble molecules interact with?
Intracellular receptors (e.g., estrogen receptor).
What do intracellular receptors do when activated?
Drive different signaling pathways.
Are receptors for water-soluble molecules membrane-bound or internal?
Membrane-bound.
Where are receptors for water-soluble molecules located and why?
On the cell membrane because water-soluble ligands cannot pass through the lipid bilayer.
Why do water-soluble molecules require membrane-bound receptors?
Because they cannot cross the plasma membrane on their own.
Where is the plasma membrane located?
It’s the outer layer of a cell that separates the internal from the external environment.
How do water-soluble hormones reach tissue cells?
They are released into the bloodstream and travel through the body.
Where do water-soluble hormones bind on the target cell?
To specific receptors on the surface of the cell.
Name some tissue types that might respond to water-soluble hormones.
Muscle cells, liver cells.
What is the role of water-soluble hormones?
Bind to receptors on the cell surface
What are common components of signal transduction pathways?
G-proteins, second messengers (e.g., cAMP), and enzymes.
What structural change occurs when a ligand binds to the receptor?
A conformational change in the receptor.
What does the conformational change allow?
Interaction with and activation of intracellular signaling proteins.
What is the result of intracellular signaling protein activation?
Amplification and relay of the signal.
What intracellular molecules might the receptor activate?
G-proteins, kinases, second messengers.
What do these molecules do after activation?
Relay and amplify the signal.
What kinds of responses can the cell have to a signal?
Changes in gene expression
Metabolic adjustments
Cell movement
Secretion of substances
What rule relates structure to signaling function?
Shape determines function.
Are receptors specific to ligands?
Yes, receptors are specific.
Why is receptor specificity important?
It ensures only target cells with the right receptor respond to a signal.
What ensures signal control despite widespread chemical release?
Only cells with matching receptors will respond.
What determines whether a receptor is present on a cell?
Dynamic expression — only certain cells express receptors at certain times.
What is required for a receptor to respond to a ligand?
The receptor must be present, and the ligand must be available.
Q: What type of molecule is insulin?
A: A hormone.
Where does insulin bind?
To the insulin receptor on muscle or liver cells.
What happens after insulin binds its receptor?
The receptor changes shape and activates a signaling cascade.
What does the cascade result in?
Insertion of glucose transporters into the cell membrane.
What is the functional outcome of glucose transporter insertion?
Increased glucose uptake and reduced blood sugar levels.
What type of receptor is GPCR?
Membrane bound receptor
What is the secondary structure of GPCRs?
Alpha helices.
What structural feature defines GPCRs?
They span the membrane 7 times via α-helices (7-transmembrane domains).
What type of residues are in the transmembrane regions of GPCRs?
Hydrophobic amino acids.
What kind of residues are on the inside of the cell in GPCRs?
Hydrophilic amino acids.
How many types of GPCRs exist?
Hundreds.
Why are GPCRs major drug targets?
They have diverse functions and are involved in many essential signaling pathways.
What processes are GPCRs involved in?
Development, sensory reception, and more.
Describe the GPCR signaling process.
Ligand binds
GPCR changes shape
G protein binds
GDP is replaced by GTP
G protein activates enzyme
Response triggered.
Why are G proteins asssociated with GPCRs (G-protein-coupled receptors)?
G proteins act as molecular switches that transmit the signal from the activated receptor to the inside of the cell.
What energy molecule is involved with G proteins?
A: GTP.
What is the state of a G-protein when the receptor is unbound?
Inactive, with GDP attached.
What happens to the receptor when a ligand binds to it?
It undergoes a conformational change.
What does the conformational change expose on the GPCR?
New amino acid residues allowing G protein binding. G protein recognizes those specific residues, binds to the GPCR, and gets activated (swapping GDP for GTP)
What replaces GDP on the G protein after activation?
GTP.
Is the nearby enzyme active at this point?
No, it is still inactive.
What does the activated G protein do next?
It dissociates from the GPCR and activates the enzyme.
Q: What does the enzyme do after being activated?
A: It elicits a cellular response.
What intrinsic activity allows G-protein deactivation?
GTPase activity.
What does GTPase activity do?
Hydrolyzes GTP to GDP and releases inorganic phosphate.
What happens to the G-protein after hydrolysis?
It becomes inactive and detaches from the enzyme.
What happens to the enzyme once G protein detaches?
The enzyme becomes inactive again.
What is the state of the G-protein in the absence of a ligand?
Bound to GDP and inactive.
What is the state of the enzyme in the absence of a ligand?
Inactive.
What structural feature do ligand-gated ion channels possess?
A gate that controls ion flow.
What is an ion channel?
A membrane protein that allows specific ions to travel through the membrane.
What is an ion channel receptor (ionotropic receptor)?
A membrane protein that opens an ion channel in response to ligand binding.
What happens to the gate when no ligand is bound?
The gate remains closed.
What causes the gate to open?
Binding of a ligand causes a conformational (shape) change in the receptor.
What does the conformational change do?
Opens the ion channel to allow ion flow.
What can the entering ions trigger in the cell?
A cellular response such as action potential or muscle contraction.
Which system relies heavily on ligand-gated ion channels?
The nervous system.