How does a cell receive a signal, and what happens as a result?
- Signaling molecule (ligand) binds noncovalently to a cellular protein (receptor) →
- Conformational change in the receptor →
- Δ activity (if receptor = enzyme) or Δ affinity for another molecule (if receptor lacks enzymatic activity)
- Messages that can't enter cells directly are bound by receptors at the surface and the information is passed on through internally generated second messengers
How does signal amplification occur?
When a ligand binds to a receptor molecule, there is often a large increase in the conc. of some intracellular second messenger molecule, which amplifies the signal.
Why is signal amplification important?
- Fewer receptors and signaling molecules are needed to get the cell to respond
- Shorter response time
- Second messengers can spread throughout cell (and even to neighboring cells through gap junctions)
How is signal concentration controlled?
Signal concentration is often controlled by feedback loops that regulate how fast the signaling molecule is produced, whereas the rate of removal (the turnover rate or half-life) is usually (but not always) constant for any one signaling molecule.
Rapid changes in signal strength require a short signal half-life (a fast rate of removal through clearance or degradation).
What are some factors in the cellular response to signals?
- Signaling molecule conc.
- # of available receptors
- Receptor affinity for the signaling molecule
- Expression of tissue- or cell-type specific second messenger systems
What is target cell adaptation with regard to signaling?
Adaptation is a change in the cell's responsiveness to a specific signal concentration. It may be accomplished by changing:
- # of available receptors: fewer receptors → less sensitive cell; more receptors → more sensitive cell
- receptor affinity for ligand: lower affinity receptor → less sensitive cell
- response sensitivity of second messenger pathways to receptor activation: smaller response to receptor occupancy → less sensitive cell
What is signal integration?
- Each cell integrates information from many signals
- One signal can bind to different receptors in different cells, or the same type of receptor can activate different second messengers in different cells
- Two signaling molecules may act through the same second messenger, so that a boost in the concentration of one signal makes the cell more sensitive to the other one
What are some types of external signal delivery, and what are their relative affinities?
Endocrine signals are carried through the bloodstream. High affinity (provided in low concentrations, have to travel a distance)
Paracrine signals are mediated to local cells. Intermediate affinity
Autocrine signals secreted by a cell that binds to receptors on the same cell. Low affinity (provided in high concentrations)
What are some classes of signaling molecules?
- Small, rapidly diffusible molecules such as NO and CO pass into cells and alter enzyme activity directly. Very short half-lives (sec)
- Hydrophobic steroids, retinoids, and thyroid hormones are usu. carried by binding proteins in the blood and pass directly thru cell membranes to bind to cytoplasmic/nuclear receptors. Relatively long half-lives (hrs-days)
- Hydrophobic eicosinoids are phospholipid-derived. Prostaglandins, prostacyclins, leukotrienes and thromboxanes. Usu. autocrine. Typical functions: inflammatory responses and blood clotting. Bind to surface receptors, have short half-lives
How do nuclear receptors act as a primary signal transduction mechanism?
Nuclear receptors activate gene transcription.
- Diversity/specificity is provided by a family of related receptor proteins (each with DNA binding and hormone binding domains)
- Each DNA binding domain recognizes a specific DNA sequence, but actual receptor binding usu. requires dimerization
- Many form heterodimers with other TFs that contribute to binding specificity
- Nuclear translocation induced by hormone binding is common
How do hydrophilic signals act as primary signal transduction mechanisms?