Cell Signals and Signal Transduction Flashcards
What are the three stages of cell signaling?
- Reception
- Transduction
- Response
What are signals?
Signals are ions or molecules that directly or indirectly regulate protein function by altering their shape or conformation, thus activating or inactivating them.
Where does epinephrine come from?
Epinephrine is secreted by the adrenal glands above the kidneys.
Name two examples of cell communication via direct contact (local signaling).
- Gap junctions in animal cells.
- Plasmodesmata in plant cells.
What are gap junctions and plasmodesmata?
Gap junctions and plasmodesmata are channels that join two cells so that you can have the free transfer of molecules from the cytoplasm of one cell to the other.
Receptor-ligand interaction is an example of what type of cell communication?
Direct contact (local signaling).
What is paracrine signaling?
A secreting cell acts on nearby target cells by secreting molecules that are local regulators (growth factors, nitric oxide, for example). Operates on the range of µm.
What is synaptic signaling?
An electrical signal traveling across a nerve cell induces the release of neurotransmitters (serotonin, dopamine, for example) into a synapse, stimulating the target cell, such as a muscle or nerve cell. Operates on the range of nm.
What are the two types of cell communication that do not require direct contact but must be nearby?
- Paracrine signaling
- Synaptic signaling
What type of cell communication happens over long distances?
Endocrine (hormonal) signaling.
How does endocrine signaling work?
Specialized endocrine cells (sender cells) secrete hormones (insulin, glucagon, etc) into body fluids, often blood. Hormones travel via the circulatory system (blood) and reach virtually all cells in the body, but are bound only by some cells (target cells).
How does autocrine signaling work?
A secreted molecule diffuses locally and triggers a response in the cell that secretes it. The cell communicates with itself.
How does neuroendocrine signaling work?
A nerve cell releases neurohormones that diffuse into the bloodstream and trigger responses in target cells elsewhere in the body (antidiuretic hormone, oxytocin, etc).
How is neuroendocrine signaling related to endocrine signaling?
The process is essentially the same as endocrine signaling (release of a hormone to trigger a response), but the sending cell is a neuron that releases a neurohormone.
In Sutherland’s experiment, what did he know prior to the experiment?
He knew epinephrine triggers the fight or flight response and that it interacts with the liver cells. In response to epinephrine, the liver cells secrete glucose. He also knew there was an enzyme in the liver called glycogen phosphorylase.
What is the role of glycogen phosphorylase in the liver?
This enzyme is responsible for breaking down glycogen to secrete glucose into the bloodstream.
Describe Sutherland’s first in vitro experiment.
First, he purified epinephrine and glycogen phosphorylase. He put the two with glycogen to see what would happen. When he mixed epinephrine and glycogen phosphorylase, nothing happened; the glycogen did not break down.
Describe Sutherland’s second in vitro experiment.
Instead of mixing epinephrine with glycogen phosphorylase, he mixed it with adipocytes (liver cells he had purified). Since those adipocytes had glycogen phosphorylase on the inside, he saw glycogen breakdown.
Interpret the results of Sutherland’s experiment.
The epinephrine was not interacting directly with glycogen phosphorylase. Instead, there have to be intermediate steps that were not present in the first mixture. Essentially, Sutherland discovered signal transduction.
What two things do you need for reception?
- A signaling molecule (first messenger)
- A receptor that can specifically recognize the signaling molecule.
How does reception occur?
The signaling molecule binds the receptor, which initiates a conformational change that triggers a response in the cell.
What is a signal transduction cascade?
This is the response to reception inside the cell during signal transduction. One thing activates another, which activates another, and so on. If any intermediate step is removed, the process will not work.
Name an example of a cellular response to signal transduction.
- Activate or deactivate a protein or enzyme.
- Alter gene expression (turn on/off specific genes).
Describe the process of a secreted signal that cannot cross the plasma membrane.
The signal (often a water-soluble hormone) is secreted via exocytosis by the sending cell. If endocrine, it enters the bloodstream. If paracrine, it does not. Then the signal binds a cell-surface receptor.
Describe the process of a secreted signal that can cross the plasma membrane.
Small hydrophobic molecules can cross the plasma membrane because it is lipid-based. Then they bind a receptor inside the cell. This allows them to alter gene expression, making them essentially transcription factors.
Why do hydrophobic endocrine signals need to use transport proteins in the blood?
Blood is water-based, making it difficult for hydrophobic signals to move in them due to their hydrophobicity.
What are the three main kinds of cell-surface receptors?
- G protein-coupled receptors (GPCRs)
- Receptor tyrosine kinases (RTKs)
- Ion channel receptors.
What is the most common type of cell surface receptor?
GPCRs. The human genome encodes for about 800 of them. That means about 4% of the genome is for GPCRs.
How many RTKs does the human genome encode for?
58.
How many genes encode for ion channel receptors?
About 300 split between ligand-gated and voltage-gated channels.
Describe the basic characteristics of GPCRs.
GPCRs contain seven transmembrane domains and function by interacting with G-proteins.
Describe the basic characteristics of G proteins.
They are membrane proteins that bind energy-rich guanine nucleotides: GDP and GTP. They are composed of an a, B, and y subunit. Found inside the cell.
Which G protein subunit binds GDP/GTP?
The a subunit.
How does a first messenger interact with a GPCR?
It binds the binding site outside the cell and never enters the cytoplasm. This causes a conformational change inside the cell which binds the G protein.
Which G protein subunits are anchored to the membrane and which are not?
The a and y subunits are anchored but the B subunit is not.
Describe the G protein in its inactive state.
In its inactive state, the a subunit is coupled to GDP.
What causes the a subunit to displace the GDP it is coupled to with a GTP?
The first messenger binds the GPCR outside the cell, triggering a conformational change in the G protein. This change causes the G protein to displace the GDP it was bound to and exchange it for a GTP. This activates the G protein.
What happens to the a subunit when the G protein binds a GTP?
The a subunit, bound to the GTP, dissociates from the B and y subunits. This frees the a subunit to diffuse along the membrane to activate its next target by binding to a specific enzyme.
What happens to the enzyme bound by the a subunit?
It changes conformation and becomes active, leading to a cellular response.
How does the fact that the G protein has its own enzymatic activity affect the inactivation of the signal cascade?
This allows the signal cascade to be inactivated. The a subunit of the G protein hydrolyzes GTP to GDP, inactivating both itself and the enzyme. It then dissociates from the enzyme.
After dissociating from the inactivated enzyme, what does the G protein do?
It binds to its partners: the B and y subunits of the G protein. This allows it to be used again.
Describe the basic characteristics of RTKs.
- Plasma membrane receptors with enzymatic activity.
- RTKs catalyze the transfer of a phosphate group from ATP to tyrosine residues on a substrate protein.
- RTKs can simultaneously activate multiple signal transduction pathways.
How do RTKs differ from GPCRs?
RTKs are enzymes while GPCRs are not. They are less common than GPCRs, but they can activate multiple pathways at the same time.
What do kinases do?
They phosphorylate other proteins.
What is the inactive state of RTKs?
When the RTK is in its monomer form, it is inactive.
Describe the monomers of RTKs.
Each monomer has a ligand binding site, a membrane-spanning a-helix, and an intracellular tail with tyrosine residues.
What activates RTKs?
Ligands bind the receptors of the monomers, causing them to dimerize. Dimerization activates the tyrosine kinase region of each monomer, activating enzymatic activity.
