Signaling Flashcards
Ligands and Receptors
- signaling requires activation of a receptor, usually through an interaction with another molecule, called a ligand
- ligands take many forms, receptors are proteins
- ligand-receptor interactions are non-covalent (reversible binding)
- ligand binding induces a change in receptor conformation or induces dimerization of the receptor protein
Signaling through conformational change
- receptor is either cell-surface of intracellular
- binding changes the shape of the receptor and alters is function by changing enzyme activity or binding affinity for something else
- activated receptor may change the cell
Signal Amplification
usually involves second messenger molecules.
- activate one receptor makes many second messengers to get a response
- response occurs faster than without amp
- some second messengers can diffuse through the cytoplasm
Why don’t all cells respond the same way to an extracellular signal?
- signal concentrations are variable (hormones)
- the number of available receptors changes
- intracellular second messenger systems are different
- types of receptors expressed in different cells are different
Controlling concentration of an extracellular signal
- LOOK AT PICTURES!*
- concentration is the balance between synthesis and degredation
- in most cases rate of removal is constant, and to change concentration you change rate of synthesis
- fast degradation= short half life= fast changes in concentration
- slow degradation= long half life= slow changes in concentration
Changing number of receptors
- LOOK AT GRAPH!*
- increasing receptors increases sensitivity to ligands
- increasing affinity means you dont need as many receptors but have high binding rates at lower concentrations
Cellular Adaptation
changing the response to a constant concentration of ligand
- prolonged receptor activation may cause changes that desensitize receptors (reduce their response)
- Endocytosis can remove receptors from surface
- Second messengers can change the rate of transcription of the receptor gene, leading to changes in the number of receptors on the cell surface
Different Responses of Cells
- Same ligand and receptor cause different secondary pathways and therefore different responses-heart cell and salivary gland cell
- Same ligand can bind to different receptors in different cell types
Signal Integration
- each cell integrates information from many signals
- one signal can bind to different receptors in different cells
- two signaling molecules may act through the same second messenger so that a boost in concentration in one signal makes the cell more sensitive to the other one
ex of signals: survive, divide, differentiate. nothing =apoptosis
Routes of Delivery
Endocrine, Paracrine, Neuronal, Contact-Dependent
Endocrine
carried through the bloodstream- low concentration since its spread out so need highest affinity
Paracrine
from one cell to another cell. distance is slightly smaller so concentration is slightly higher so intermediate affinity
Neuronal
from neuron to neuron across a synapse. highest concentration and shortest distance to relatively low affinity
Contact dependent
through adhesions and cell-cell and cell-matrix junctions
Classes of signaling molecules
- small diffusible molecules (NO, CO)
- hydrophobic molecules (steriods and eiconsinoids [bind to two receptor types])
- hydrophilic molecules (peptides, aa derivatives- glutamate)
- sensory signals (taste, smell)
NO in blood
AP causes nitric oxide to be released in endothelial cells, diffuses across membranes, binds to target proteins (phosphodiesterase) and relaxes smooth muscle.
small molecules have shorter half lives
Steriods
Bind to nuclear receptors (pass thru cell membranes) and are carried by binding proteins in the blood. longer half lives.
Eicosinoids
derived from phospholipids and include prostaglandins, prostacyclins, leukotrienes and thromboxanes. function in inflammatory responses and blood clotting.
lipid soluble but bind to surface receptors, have short half lives, and usually act as autocrine (secreted by cell and bind to same cell).
are inhibited by aspirin and other NSAIDs, vioxx, and cortisone
Hydrophilic molecules
peptides, aa derivatives
bind to surface cell receptors and have short half lives.
sensory signals
EM radiation, vibration chemicals (sound, smell, taste). sensory receptors are cell surface molecules. not part of cell-cell but do rely on receptors and intracellular response mechanisms
Steroids and signal transduction
-bind to receptor (intracellular) and change conformation so DNA binding site on receptor is open so it can change transcription rate of a gene (via promoter sequence)
Partner TF
May be a TF already on promoter region
-ligand binds to receptor and complex binds to TF on promoter to alter transcription rate
Signaling by transmembrane surface receptors
- ion channel linked- signal binds and opens ion channel
- G-protein linked receptors- signal binds and activates G protein that activates enzyme
- enzyme linked- signal in dimer or single molecule- binds to enzyme and activates domain or enzyme
Gated Channels
- voltage gated
- ligand gated (extra or intracellular)
- stress gated
- ex-nerve synapse. Ca comes in (voltage gated), activates exocytosis to release NT, which binds to another gate (NT gated) across synapse
