Cell Signaling/Communication Flashcards
Cell communication overview
What do gap junctions between cells allow?
- Allow small molecules to pass back and fort
- If one cell’s membrane potential is changed, that information can be directly passed on to the cell it’s coupled with because if cell number one depolarizes, that will immediately impact cell number two because they’re electrically coupled (as well ass chemically coupled).
Direct surface protein interaction
- Still intimate but no channel between the two like with gap junctions
- A protein on the surface of one cell is binding to and interacting with protein on the surface of the second cell
- In doing so, it’s initiating changes on the intracellular side
Chemical messengers
- A little more distant but still within the range of diffusion
- Molecule is released into the extracellular fluid, it’s free to diffuse, and in this case, it’s only impacting the cells that are nearby
- Can get into the circulatory system
Autocrine
- Releasing a chemical messenger that binds to a receptor on your own cell body surface and changing the internal environment in the same cell
- Acts as a feedback system, telling the cell that it’s releasing too much of that messenger
Paracrine
Impacting cells in the nearby region within the limited range of diffusion
Two categories of cell communication
Classes of chemical messengers (don’t need to know specific names- point is to show the diversity of messengers
Difference between hormone and neurotransmitter
- If it’s floating around in the blood, it’s a hormone.
- If it’s released at synapses from one neuron onto another, or from a neuron onto a gland or muscle, it’s a neurotransmitter.
- The one exception is amino acids. They can only be used as a neurotransmitter. They can’t be used to send messages through the bloodstream because there’s already so many amino acids in the bloodstream
Steps in chemical transmission
- Ligand released
- Ligand binds receptor protein
- Receptor protein undergoes conformational change that leads to:
- Ion channels in membrane opening or closing OR
- Second Messenger increase or decrease inside cell that could have different effects in the cell
Diagram of binding sites of messengers
- The receptor has an affinity for a certain chemical messenger
- When the messenger binds, the intracellular side of the receptor will change shape and something will happen e.g. change in internal state of cell
- The higher the concentration of chemical messenger, the more binding events there will be per second, and the stronger the signal will be to the cell (Cell A)
Agonists and antagonists are both ___
Exogenous
They come from outside the body e.g. a drug, toxin, poison
Agonist
Exogenous substance that binds to a receptor and activates it
Antagonist
An exogenous substance that binds to a receptor and blocks it
Down-regulation
Decrease in the number of receptors in the target cell (relates to homeostasis)
Lipid-soluble messengers
- Lipid soluble- can easily diffuse through the membrane
- Most are synthesized on demand (except thyroid hormones)
- Freely diffuse from blood to tissue
- May bind to plasma proteins to maintain higher amounts of circulating hormone
- Do not require membrane receptor
Have receptors in cytoplasm or nucleus - Typically regulate slower responses that mediate transcription/translation
Diagram showing different types of categories of receptors
dIn a), the receptor is an ion channel, so when the ligan binds, it changes the shape of the channel, allowing the ion to go through
b) Tyrosine kinase: the receptor itself is a kinase (a protein that phosphorylates another protein (attaches the phosphate group from ATP and covalently bonds it to that protein). When the first messenger binds on the extracellular side, the intracellular domain undergoes a conformational change, such that the enzymatic activity goes up, and it starts phosphorylation proteins
d) G-protein coupled receptors
G- protein coupled receptor
- Binding of the first messenger on the extracellular side initiates a conformational change on the intracellular side that brings alpha, beta, and gamma subunits all together
- The key thing (why it’s called a G-protein) is that it binds GTP
- The alpha subunit can bind GDP or GTP. When GDP is bound, the alpha, beta, and gamma subunits hold together and associate with the receptor
- When the first messenger binds on the extracellular side, it changes the shape of the alpha subunit such that it gives up the GDP and GTP binds
- When GTP binds to the alpha subunit, it no longer associates with beta and gamma (its affinity for them decreases), it separates, and both beta, gamma, and alpha are free to move
- That freedom allows alpha to activate the effector protein. The alpha subunit becomes activated, and interacts with the nearby protein (adenylyl cyclase)
- Adenylyl cyclase converts ATP into cAMP (second messenger), which is used to activate a cAMP-dependent protein kinase, which phosphorylates a protein to generate a cell response
- Adenylyl cyclase does this repetitively until the alpha subunit unbinds. It unbinds when GTP is hydrolyzed back into GDP (alpha subunit is an enzyme)
- When GDP is bound, it dissociates from the effector protein, reassociates with beta and gamma and the receptor
Compartmentalization
How can two different signaling pathways illicit two different cellular responses using the same second messenger?
- Each receptor is surrounded by different effector proteins, protein kinases and proteins that are phosphorylated
- This complement of nearby proteins is determined by chaperone proteins and anchoring proteins (e.g. PKA anchoring proteins or AKAP’s
