Cellular Communication Flashcards
why is cell communication is necessary?
to control and coordinate responses of multiple organs to different scenarios (e.g. fight/flight, sleep, fed, starved)
the cascade of reactions in an organism in response to a signal
transduction pathway
Types of signals
- Endocrine Factors (hormones) - travel in the blood
- Paracrine/autocrine factors - released locally. Do not travel in the blood.
- Neurotransmitters - released at a synapse, which is defined as a narrow space between a nerve/nerve or a nerve/muscle
Hormone definition
It must arise from one organ, travel in the blood to a distant organ.
Paracrine factors examples
growth factors EGF, NGF, PDGF, HGF, FGF
Neurotransmitter examples
acetylcholine, norepinephrine, serotonin
Endocrine hormone examples
peptides, steroids, modified amino acids
Acetylcholine
An example of a signal that can have multiple effects in the body depending on which receptor it hits (which depends on the cell type) and transduction mechanism it initiates. Ex: In a heart muscle, acetylcholine decreases the rate and force of contractions; in the salivary gland, it causes exocytosis of salivary enzymes; in skeletal muscle, it causes muscle contraction
Types of Receptors
- Nuclear Hormone receptors (for steroid hormones)
- Ligand-gated ion channels
- G-protein coupled receptors (GPCR or 7TM)
- Enzyme-linked receptors
a. Membrane receptors that dimerize then recruit protein kinases
b. Membrane receptors that dimerize and are protein kinases
Transduction Mechanisms
Differ for each class of receptor
Nuclear Hormone receptors
The only category of receptor that is not membrane-bound. It could be in the cytoplasm or in the nucleus and its ligand is hydrophobic, so it can diffuse across cell membranes.
Nuclear Hormone receptors are transcription factors that contain a hormone-binding domain and a DNA binding domain. The hormone-receptor complex recognizes a specific nucleotide sequence in DNA promotor elements to activate transcription of a gene.
Hormones that use nuclear hormone receptors
cortisol, cortisone, estrogen, testosterone, thyroxine, retinoic acid (vitamin A derivative); 1,2,5 dihydroxycholecalciferol (vitamin D derivative)
hormone and nuclear hormone receptor function
the hormone diffuses through the cell membrane due to hydrophobicity. Its nuclear hormone receptor is in the cytoplasm or nucleus. When the two bind, the complex moves into nucleus if necessary and they find the target sequence to activate or repress some target gene.
Ligand-gated ion channels
The binding of a ligand to the membrane-bound receptor leads to the receptor opening to allow ions to come in. ex: acetylcholine binds to an ion channel for sodium ions and allows sodium to rush into the cell with its concentration gradient. This process is also a specific type of transduction mechanism whereby the voltage change leads to neuronal signaling and muscle contraction.
Action potential
The name of the nerve impulse. The nerve impulse comes from the depolarization of the membrane potential that gets passed down from one end of the cell to the other.
G-protein coupled receptors structure
Every G-protein coupled receptor has 7 transmembrane helices. It has a ligand binding site and some loops that loop into cytoplasmic side that will interact with G proteins
G-protein receptor functions
The signal is transducer when the signal-receptor complex interacts with trimeric G protein on the cytoplasmic face of the plasma membrane, causing GDP to drop out allowing GTP to bind. This receptor class receives diverse signals such as odors, light, hormones, and neurotransmitters.
Each thing we smell has a unique G protein receptor.
G protein structure
Has 3 subunits:
- alpha
- beta
- gamma
Alpha unit alternately binds GDP or GTP.
G protein and receptor process of transduction for epinephrine
- -The G-protein receptor receives a signal from outside the cell that causes a conformational shape in the receptor.
- -When the receptor changes conformation, the G protein inside the cell recognizes this and binds to the receptor. When the G protein binds to the receptor, it causes GDP to fall out of the alpha subunit and GTP can bind in its place.
- -GTP binding causes the subunits to dissociate from each other, so the alpha subunit is free from the beta and gamma. (Beta and gamma stay together).
- -Alpha subunit is now known as alpha-S (in its stimulated form).
- -Alpha-S then stimulates the integral membrane enzyme, adenylyl cyclase.
- -Activation of cyclase catalyzes the formation of cAMP from ATP and H2O.
- -cAMP is the “second messenger,” which is mobile and can act in epinephrine’s stead
- -cAMP can act on other enzymes or transcription factors to change behaviors in the cell
adenylyl cyclase
initiates the reaction: ATP + H2O –> cAMP + PPi
Makes cyclic AMP out of ATP.
Is turned on by alpha-S (alpha subunit of G protein that has GTP bound so it’s in its “stimulated” form).
cyclic AMP phosphodiesterase
Turns cyclic AMP back into AMP
What does cyclic AMP do as a secondary messenger?
cAMP allosterically activates protein kinase A.
Protein kinase A
phosphorylates protein targets (i.e. transcription factors and enzymes) that alter physiological functions of the cell. (Once phosphorylated, these proteins may be activated.) PKA can translocate to the nucleus and phosphorylate transcription factors in the nucleus that alter gene expression.
Protein kinase A tells the cell to get glucose out of glycogen b/c we don’t have enough in the blood.
How do we shut down the epinephrine-initiatated pathway?
- Epinephrine might stop being secreted by adrenal glands and once it drops in concentration, there won’t be as much to replace the epinephrine that is dissociating from receptors
- The alpha subunit is actually an enzyme that will very slowly hydrolyze GTP. So the alpha subunit will eventually remove the phosphate from GTP to leave GDP and switch itself off.
- phosphodiesterase can clip cAMP back to AMP
