Cell communication Flashcards
Essential parts of a cell signaling pathway
Signal (hormone, neurotransmitter, chemical) Receptor Signaling molecule Effector (causes change) Secondary messenger (ex- Ca+2)
Importance of cell communication
Differentiation Survival Coordination of systems Gene expression and regulation Grow/reproduce Transportation Movement
Signal transduction
Converting one type of signal to another
Extracellular signal converted into intracellular signal
Signal arrives at cell Designated receptor perceives signal Signal is transmitted into cell Signal is passed to various signaling components Signal arrives at destination Signal is turned off
First messenger
Extracellular substance/molecule that initiates signal
Receptor
Binds specifically to first messenger
Ligand
Molecule that binds to another
Cascade
Events that happen in a specific order after a stimulus (first messenger binds to receptor)
Second messenger
Intermediate non-protein molecules that relay signal
Response
What happens to the cell (change in gene expression and/or change in protein activity)
Effector protein
Affects the behavior of a cell
Mating pathway of yeast
Mating type a has a factor (mating pheromone)
a factor binds to protein, triggering cell arrest (use energy to fuse rather than to grow) and then cell fusion
Common themes in cell signaling
Specificity: a cell is bombarded with signals (can choose to respond or to ignore)
Amplification: small amount of signal can have big effects on a cell
Cross talk: many signaling cascades happening at once
Concentration: how the cell concentrates and compartmentalizes a signal
Signaling molecules
Hormones Neurotransmitters 2nd messengers (Ca+2) Growth factors Pheromones Amino acids Proteins Ions Nucleic acids Lipids
Endocrine signaling
Endocrine cells make signaling molecules (hormones)
Hormone travels through bloodstream to target tissue
Target cells recognize signal
Insulin signaling
Example of endocrine signaling
Sugar in bloodstream triggers release of insulin from pancreas
Insulin travels to target (example: muscle) and causes target cells to take up glucose
Paracrine signaling
Signal is made in one cell and diffuses through extracellular fluid to target cell
Epidermal growth factor
Protein that is made in one cell and triggers cell proliferation in a different cell
Example of paracrine signaling
Autocrine signaling
Signal is made, secreted, and recognized by the same cell
Reinforcement of signal
Neuronal signaling
Neurotransmitter is made by neuron
Travels down axon and crosses synapse
Received by target cell
Juxtracrine signaling (contact-dependent signaling)
Involves direct physical contact of 2 cells
1 cell has receptor anchored in plasma membrane
Other cell has signal anchored in membrane
Nerve cell formation
Nerve cell develops from unspecialized epithelial cells in embryo
Nerve cell has membrane-bound inhibitory signal protein (Delta) that attaches to receptor protein (Notch) bound to epithelial cells
Epithelial cells are inhibited from becoming neurons
Varying effects of acetylcholine
Heart muscle cell: decreased rate and force of contraction
Salivary gland cell: secretion of saliva
Skeletal muscle cell: contraction
Cell receiving multiple signals at once
1 signal can modify another signal (cross talk)
3 survival signals: survive
3 survival signals + 2 grow and divide signals: grow and divide
No survival signals: death
Types of cell responses to signal
Fast: altered protein function
Slow: altered protein synthesis
2 types of receptors
Cell surface receptors (signal is large hydrophilic molecule- can't cross membrane) Intracellular receptors (signal is small hydrophobic molecule- can cross membrane)
Small hydrophobic hormones
Can cross membrane
Estradiol, testosterone, cortisol
Intracellular receptors and response elements
Cortisol (stress hormone) binds to nuclear receptor protein, causing conformational change that activates protein
Activated receptor-cortisol complex moves into nucleus
Complex binds to regulatory region of target gene (hormone response element) and activates transcription
Dissolved gas signals
NO (nitric oxide)
Acetylcholine binds to endothelial cell -> amino acid arginine releases NO -> NO diffuses across membranes -> binds to target protein of smooth muscle cell, causing relaxation of cell
Roles of intracellular signaling molecules
Relay and spread signal throughout cell Amplify signal Integrate several signals Distribute signal to more than 1 pathway Compartmentalization of signal (scaffolding, cytoplasmic hotspots, lipid rafts)
Signaling molecules acting as molecular switches
Phosphorylation either activates or deactivates molecule
3 types of cell receptors
Ion channel coupled receptors
G-protein coupled receptors
Enzyme coupled receptors
Ion channel coupled receptors
Signal molecule binds to ligand-gated channel
Channel opens, allowing ions across cell membrane into cytosol
G-protein
Protein modulated by GTP
G-protein coupled receptors (GPCRs)
Receptor has 7 transmembrane domains
Signal binds to GPCR
Heterotrimeric G-protein’s GDP is transformed into GTP
Activated alpha subunit (GTP bound) separates from activated beta-gamma complex
Turn off signal: hydrolyze GTP to GDP
Alpha subunit re-binds to beta-gamma complex
Kinase
Enzyme that phosphorylates molecules
Cell signaling: phosphorylation activates molecules
Regulation of ion channels by G-proteins
Activated alpha subunit separates from activated beta-gamma complex
Beta-gamma complex combines with ligand-gated ion channel, opening it
Activation of enzymes by G-proteins
Activated alpha subunit binds to adenyl cyclase
Adenyl cyclase catalyzes transformation of ATP to cyclic AMP
Cyclic AMP
Secondary messenger
Synthesized from ATP
Cyclic AMP-dependent protein kinase a (PKA) in neurons
Initial activation: adrenaline
GPCR activates alpha subunit, which activates adenyl cyclase, which turns ATP into cAMP
cAMP activates PKA
PKA enters nucleus and activates transcription regulator
Transcription of gene
cAMP-dependent PKA in skeletal muscle
Initial activation: adrenaline
GPCR activates alpha subunit, which activates adenyl cyclase, which turns ATP into cAMP
cAMP activates PKA
PKA activates phosphorylase kinase, which activates glycogen phosphorylase
Glycogen breakdown
Phospholipids as secondary messengers
Signal activates GPCR, which activates alpha subunit, which activates phospholipase C
Phospholipase C cleaves phospholipid into 2 parts: diacylglycerol (stays in membrane) and IP3 (secondary messenger)
IP3 binds to ligand-gated Ca+2 channel in ER, causing it to open
Calmodulin
Binds to Ca+2 -> conformation change -> activation of another kinase
Enzyme-coupled receptors
Dimer molecule binds to receptor tyrosine kinase (RTK), activating it
Autophosphorylation of RTK: one molecule of RTK phosphorylates other (2 molecules present)
RTK becomes phosphotyrosine and is recognized by signaling proteins
Ras Pathway
- Signal molecule binds to RTK
- RTK is activated
- RTK activates Ras-activating protein
- GDP is phosphorylated into GTP and binds to Ras protein, activating it
- Activated Ras protein binds to MAP (mitogen-activating protein) kinase kinase kinase
- MAP kinase kinase kinase hydrolyzes ATP and phosphorylates MAP kinase kinase, activating it
- MAP kinase kinase hydrolyzes ATP and phosphorylates MAP kinase, activating it
- MAP kinase hydrolyzes ATP and phosphorylates either a protein or a transcription factor, causing either changes in protein activity or gene expression