Lec 20: Mechanisms of Cell Communication Flashcards
Hormones
Extracellular signal molecule that is secreted and transported via the bloodstream (in animals) or the sap (in plants) to target tissues on which is exerts a specific effect.
In animals, the cells that produce hormones are called endocrine cells
Paracrine signaling
signals that, instead of entering the bloodstream, diffuse locally through the extracellular fluid. They act as local mediators
Local mediators
secreted signal molecule that acts at a short range on adjacent cells.
Ex molecules that regulate inflammation at the site of an infection, or that control cell proliferation in a healing wound
autocrine signaling
when cells can respond to their own paracrine signals. Sometimes this is how cancer cells proliferate
Neuronal signaling
nerve cells deliver messages to specific target cells
contact-dependent signaling
when cells make direct physical contact through signal molecules lodged in the plasma membrane of the target cell
Four types of intracellular communication
1) Endocrine
2) Paracrine
3) Neuronal
4) Contact-dependent
Receptor
Protein that recognizes and responds to a specific signal molecule
Classes of extracellular signal molecule
1) molecules that are too large or hydrophilic to cross the extracellular membrane. They rely on receptors on the surface of a targeting cell.
2) Molecules that are small and hydrophobic and call pass through the cell membrane and bind to intracellular receptor proteins
Do all cells respond the same way to all extracellular signals?
No, cells can specialize which receptors they have, and can even have receptors that respond to the same molecule in a different way than another cell. (Acetylcholine makes the heart beat slower and makes the salivary glands secrete more saliva, and makes skeletal muscles contract)
Intracellular signaling pathways
Once a receptor protein recognizes a signal molecule, it must generate a different intracellular signal in response that gets passed along until the desires effect happens (the response of the cell).
1) relay signal onward and help spread it through the cell
2) amplify the signal received
3) detect different signals and integrate them into one response
4) distribute the signals to more than one effector protein, which creates branches in the information flow and evokes a complex response
5) They can engage in feedback: modulating the response by regulating the activity of the components upstream in the signalling pathway
Molecular switches
intracellular signaling protein that toggles between an active and inactive state in response to receiving a signal. They can stimulate or repress other proteins in the signaling pathway, and will persist in the active or inactive state until something else switches them off
1) Proteins that are activated or inactivated by phosphorylation: the phosphatase does not generate back an ATP, it costs energy to transmit information
2) GTP binding proteins: also costs energy when the GTP is hydrolyzed
Classes of cell-surface receptors
All bind to an extracellular signal molecule and transduce its message into one or more intracellular signaling molecules
1) Ion-channel-coupled receptors: change the permeability of the plasma membrane to selected ions. Alter the membrane potential and can start an electric current
2) G-protein-couple receptors: activate membrane-bound GTP-binding proteins, which then activate or inhibit an enzyme or an ion channel in the plasma membrane initiating an intracellular signal. (Most important drug target)
3) Enzyme-couple receptors: act as enzymes or associate with enzymes inside the cell.
G-protein-coupled receptors
Largest family of cell-surface receptors.
Thread back and forth through the cell membrane 7 times.
Activates a G protein on the cytosolic side of the plasma membrane
Regulated by GDP/GTP
action potential transmission along an axon
Both toxins ultimately activate adenylyl cyclase. However, cholera does this by activating a G protein and pertussis does this by inactivating a G protein
Receptor tyrosine kinases
usually span the cell membrane as a single alpha helix, which makes it hard to transmit information, so usually two receptors come together
Tyrosine kinase: an enzyme group that puts phosphate groups onto tyrosine
The RTKs are internalized and digested in lysosomes. They can also be switched off in a more reversible manner, by removal of activating phosphates by a tyrosine phosphorylase
turn themselves off
Basic elements found in a cell signalling pathway
speeds of different responses to signal molecules
nuclear receptors
Usually respond to steroids that can pass through the cellular membrane because they are nonpolar. Bind to a protein that can then cross into the nucleus, and as a transcription regulator
What happens once a cell’s receptor protein is activated?
The cell needs to make sure that the correct signals go through the right pathways–lots of opportunity for modulating the signal (the signalling cascade)
Intracellular signalling complexes
What is caused by a rise in intracellular cyclic AMP?
some g proteins can regulate the production of cyclic AMP
How do activated tyrosine kinases work?
they phosphorylate themselves and form an aggregate of proteins
antibodies: have two binding sites
If the RTKs can be activated by dimerization, then an antibody that can bind to two receptors at a time will be able to activate the RTK.
It is possible to deisign an antibody that block activity and prevents it from working, but sometimes it will act as an agonist and not an antagonist
Ras
Mutated in a lot of cancer; typically so that it is GTP bound and always active. it’s one of the most important drug targets
Binds to GTP much easier–which makes it become active all the time
