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____ must receive and adapt to signals from their environment.
Cells
Cells must “__________” their needs.
Communicate
What are extracellular signal molecules made by?
Own body or drugs
Receive information, ears of the cell; transmembrane proteins
Receptor proteins
What is outside the plasma membrane in a cell signaling cascade?
Extracellular signal molecule and receptor protein
What is inside the plasma membrane in a cell signaling cascade?
Intracellular signaling molecules, effector proteins, and target cell responses
Proteins that have physiological effects
Effector proteins
What are some examples of effector proteins?
Metabolic enzyme, cytoskeletal protein, and transcription regulator
What target cell response does the metabolic enzyme do?
Altered metabolism
What target cell response does the cytoskeletal protein do?
Altered cell shape or movement
What target cell response does the transcription regulator do?
Altered gene expression
Once you turn receptor on, that’s going to turn on another protein and that’s going to turn on another protein (repeats!) and this is called a __________ because it’s one thing after the next. Eventually, this will cause effects in the cell. It will do that when we get to effector proteins.
Cell signaling cascade
Long distance signaling
One cell doing the talking which releases the message, it is going to go into the bloodstream (bloodstream = everywhere!), now every cell in whole body hears it!
Endocrine
Long distance signaling
Endocrine
One cell doing the talking which releases the message, it is going to go into the bloodstream (bloodstream = everywhere!), now every cell in whole body hears it!
Endocrine
Localized signaling (within one organ)
Reaches nearby things
Does NOT go into bloodstream
Doesn’t reach every cell in body
Paracrine
Localized signaling (within one organ)
Paracrine
Does NOT go into bloodstream (doesn’t reach every cell in body!)
Paracrine
With neurons, electrical signaling
Neuronal/synaptic
Neurons fires action potential, releases neurotransmitters, binds to target cell
Neuronal/synaptic
Two cells have to be in physical contact to work
Whispering
Contact-dependent
Hormones are examples of what?
Endocrine
What is delta notch an example of?
Contact-dependent
One signaling molecule can induce different _____ on different target cells.
Responses
One signaling molecule may have several ______.
Receptors
Receptor response depends upon the _____ of the cell.
Context
What are some examples of what the acetylcholine signaling molecule can do to different cell types?
decreased rate of firing in heart cells, secretion in salivary gland cells, and contraction in skeletal muscle cell
Explain how signaling molecules like acetylcholine can affect different cell types.
Signaling molecules, like acetylcholine, have different effects depending on the cell type and that’s because a lot of things have different receptors on the cell type.
Cells just needs ______ to just stay alive.
Signals
Without cell signaling, what happens to cells?
They die (apoptosis)
Why does a cell require many signals?
Survive, and more to grow, divide, and differentiate
Every cell type displays a specific set of receptor proteins, enabling what?
To respond to a specific set of extracellular signal molecules
Cells need survival factors (signaling) or else what?
They’ll commit program cell suicide (apoptosis)
For cell types, they need even more stuff —> do you want to be an eyeball cell, liver cell, brain cell, all of that requires what?
Additional levels of communication
Grow + divide requires what?
Additional signaling
Differentiate requires what?
Different levels of communication
What cell type in the human body can live without talking to each other?
Cancer cells
Explain the “fast” pathway.
Phosphorylation turning proteins on and off
Explain the “slow” pathway.
Transcription and translation making more proteins
Why are fast pathways fast?
Turning on/off proteins that already exist
What are some examples of a fast pathway?
Phosphorylation, GTP-binding, Quaternary regulation
Why are slow pathways slow?
Have to make new proteins and that isn’t instant
In slow pathways, signal goes into _____ and that turns on/off chains and that’s going to change what proteins we make.
Nucleus
What are some examples of slow pathway effects?
Transcription, translation, deliver these proteins
Changing how we express our genes and what proteins we make
Slow pathway
Viagra blocks phosphodiesterase type 5 (PDE5) which ___________ causing prolonged relaxation of smooth muscle (vasodilation).
breaks down cGMP
Starts with __________, goes through body and we have the endothelial cells releasing nitric oxide.
sexual simulation
What does nitric oxide do with GTP?
Cyclases it into cyclic GMP, and cyclic GMP causes vessels to relax
As long as cyclic GMP is there, you are going to get winding of the vessels and that winding of the vessels allows what?
Erection
What is sildenafil, which directly touches that enzyme and stops it from working?
Phosphodiesterase type 5 (PDE5) inhibitor
If you stop Phosphodiesterase type 5 (PDE5) from working, what does that mean?
cGMP is not broken down
Does inhibiting Phosphodiesterase type 5 (PDE5) mean more or less cGMP?
More cGMP because not breaking it down
cGMP around for longer means you get ____ for longer, which is the winding of the blood vessels.
Effect
What are four things cell signaling cascades can do?
Relay, amplify, integrate, and distribute
Intracellular signaling pathways can ____ the signal onward and thereby help spread it through the cell.
Relay
Pass the signal from one to another
Relay
Intracellular signaling pathways can _____ the signal received, making it stronger, so that a few extracellular signal molecules are enough to evoke a large intracellular response.
Amplify
Make weak signal very strong!
Amplify
Intracellular signaling pathways can receive signals from more than one intracellular pathway and _____ them before relaying a signal onward.
Integrate
Taking information from different places, based on different types of feedback, compress down into one decision.
Integrate
Intracellular signaling pathways can _____ the signal to more than one signaling pathway or effector protein, creating branches in the information flow diagram and evoking a complex response.
Distribute
Gives signal to effector protein, which causes physiological effects/changes
Distribute
Always say “yes! we need more!”
Positive feedback
increase activity of signaling pathway
Positive feedback
Says “we don’t need that much”
Negative feedback
decreases activity of that signaling pathway
Negative feedback
How is homeostasis maintained?
Signaling cascades and feedback regulation
Body strives to maintain a biological ‘set-point’
body temperature, weight, receptor signaling
Homeostasis
All signaling cascades are ______ and ______ one another.
Connected and influencing
What are the three main classes of cell-surface receptors?
Ion-channel-coupled receptors, g-protein-coupled receptors, and enzyme-coupled receptors
What is the fourth class of cell-surface receptors?
Intracellular receptors
Drugs (exogenous) are effective on our cell surface receptors because they are _________ to proteins that we already made (endogenous).
Structurally similar
What is the reason drugs work?
Same shape as signaling molecules already found in our body
Extracellular signaling molecules can interact with more than one type of receptor to increase the _____ of the cellular response.
Diversity
A signaling molecule can have hundreds of different types of ______ for it.
Receptors
What are some examples of the receptors acetylcholine can have?
Ion-channel-coupled receptor and G-protein-coupled-receptor
What does an ion-channel-coupled receptor in skeletal muscle do in acetylcholine?
Increasing contractions
What does a G-protein-coupled receptor in heart muscle cells do in acetylcholine?
Decreasing rate and force of contractions
Flow of ions across the plasma membrane - changes the membrane potential and produces an electric current
Ion-channel coupled receptors
Neurotransmitters at the postsynaptic membrane
Example of Ion-channel coupled receptors
Ion-channel coupled receptors are the exact same as what ion channel?
Ligand-gated ion channels
How are Ion-channel coupled receptors different than Ligand-gated ion channels?
Uses signaling molecules instead of ligands to turn on/off
Ion-channel coupled receptors are both a _____ and ______ at the exact same time.
(Receiving information and signaling molecule is binding to it)
Receptor and ion channel
Largest family of cell-surface receptors
G-protein-coupled receptors (GPCRs)
Where the vast majority of drugs work!
G-protein-coupled receptors (GPCRs)
About half of all known drugs work through ________.
G-protein-coupled receptors (GPCRs)
G-protein-coupled receptors (GPCRs) are _____ proteins.
Transmembrane
G-protein-coupled receptors (GPCRs) are _____ into membrane as they’re being made.
Stitched
G proteins (alpha and gamma) are associated with the ______.
Membrane
What relays the signal from outside to inside?
Conformational changes
The ______ stays active while signal is bound, activating many ______ (amplification!)
Receptor, G proteins
What is the G protein made of?
Alpha, beta, and gamma subunits
Explain the G protein’s structure when it’s off.
Alpha/gamma/beta are stuck together, making one big quaternary structure
G protein is ______. (physically connected to membrane)
Lipid-linked
When G protein is off, what is it bound to?
GDP
Low energy form
GDP
G protein needs ________ to bind
Then turns _____ on
Changes shape of ________ protein.
Signaling molecule, receptor, transmembrane
Only signaling molecule that fits into the _____ can fit, which changes shape and turns G protein ___.
Receptor, on
What happens when G proteins turn on?
Release GDP and as soon as they have an open space, they’re going to suck up GTP (high energy)
What happens when GTP is sucked up by a G protein?
GTP binds to the alpha subunit and that separates from the beta and gamma complex