Ch 6: Communication Flashcards
Methods of cell-to-cell communication
- Gap junctions
- Contact-dependent signals
- Cells release messengers to the ECF
Gap junctions
Direct cytoplasmic transfer b/t adjacent cells
*aka communicating junction
- short distance
- transfer both chemical and electrical signals
Contact-dependent signals
Surface to surface contact b/t membranes
- proteins embedded in membrane
- short distance
Cells release messengers to the ECF
- Long-distance communication
—hormones, neurohormones, & neurotransmitters - Local communication
—paracrine & autocrine
*can go long distances
Cellular messengers
- Hormones
- Neurotransmitters
- Neurohormones
- Paracrine agent
- Autocrine agent
Hormones
Released from tissue and travels to target cell thru blood
Neurotransmitters
Released from neurons to adjacent effector
- only from synapse to adjacent cell
Neurohormones
Released from neuron & travels to target cell thru blood
Paracrine agent
Released into interstitial fluid & affects neighboring target cell
Autocrine agent
Released into interstitial fluid & affects the cell that released it
Communication b/t cells also accomplished by?
SIGNAL MOLECULES (intracellular chemical messenger) & RECEPTOR
Receptors
Protein associated w/ the membrane or cellular interior which will bind a chemical messenger & exert an effect
*protein binding to a ligand
- highly specific
- high affinity for specific messenger
- can be saturated or blocked
Receptors can undergo…
- Down-regulation
- Up-regulation
Down-regulation
Decrease in receptor # in response to chronic elevated levels of messenger
- ex: Type II diabetes
Up-regulation
Increase in receptor # in response to chronic low levels of messengers
Routes of messenger action
- Lipophilic messengers
- Lipophobic messengers
Lipophilic messengers
Diffuse directly thru the membrane to an internal receptor
- lipophilic generally hydrophobic
- contains binding protein (amphipathic)
- relatively slow response, but persist in body
—ex: steroid (modifies transcription)
Lipophobic messengers
Must enter cell thru transport or bind to a surface receptor
- signal transduction
- fast responses (internal), but degrades quickly
- generally hydrophilic
- must bind noncovalently, causing protein to flex
Signal transduction
Message is conveyed from outside of cell to a new signal inside of the cell which then creates a cellular response
- converts one form of signal into a different form
Signal transduction benefits the cell thru?
- Signal amplification (start small get big)
- Mutli-tasking (more than one effect)
Transducers
Convert extracellular signals into intracellular messages which create a response
Lipophobic messengers act on 4 types of membrane receptors
- Ligand-gated receptor channels
- Receptor enzymes
- GTP-binding proteins
- Integrin receptors
Ligand-gated receptor channels
Receptor proteins that can act as an ion channel
Receptor enzymes
Receptor acts as an enzyme & messenger binding initiates enzymatic activity resulting in cellular response
GTP-binding proteins
Messenger activates a G-protein which opens an ion channel or activates an enzyme
Integrin receptors
Messenger binding causes a change in the cytoskeleton
Mechanisms of signal transduction (non-covalent binding)
- Messenger binds to ligand-gated channel
- Receptor enzymes
—Kinase receptors - GTP-binding proteins
Messenger binds to ligand-gated channel
Now permeable to ion flux
- nicotinic, GABA, glycine
- depolarize, hyperpolarize, repolarize
Receptor enzymes
When activated, receptor enzymes act as enzymes to alter cytoplasmic proteins
- allosteric activation
Receptor enzymes: kinase receptors
Kinase receptors include many families of growth factors including: epidermal GF, platelet-derived GF, fibroblasts & insulin
- covalent modulation = phosphorylation of protein
GTP-binding proteins (2nd messenger systems/ G protein coupled receptors [GPCR])
In a second messenger system, the intracellular messenger (or 1st messenger) binds non-covalently to a surface protein & activates a G-protein that initiates an internal chemical (or 2nd messenger) that initiates the cell’s response
- may open a channel or activate an enzyme
- “extra steps”
2nd messengers
- Cyclic AMP (cAMP)
- Phospholipase C (GPCR)
CAMs
Transfer signals in both directions
Beta 2-Adrenergic Receptor
Transmembrane protein that noncovalently binds to epinephrine (adrenaline)
*signal transduction
Steroid hormone influences?
Transcription
- slower responses related to changes in gene activity
cAMP system (detail)
- Signal molecule binds to G protein-linked receptor, which activates the G protein
- G protein turns on adenylyl cyclase, an amplifier enzyme
- Adenylyl cyclase converts ATP to cyclic AMP
- cAMP (2nd messenger) activates protein kinase A
- Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response
ATP to cAMP to AMP
Phosphate group originally on C5, now on C3
- cAMP is an intermediate
Cells prefer ATP
Energy is from phosphate to phosphate bond
- not influenced by bases
GPCR: The Phospholipase C system
*Doesn’t attack phospholipids at random, only attacks one type
1 Signal molecule activates receptor and associated G protein
2. G protein activates phospholipase C (PL-C), an amplifier enzyme
3. PL-C converts membrane phospholipids into diacylglycerol (DAG), which remains in the membrane, and IP3, which diffuses into the cytoplasm
4. DAG activates protein kinase C (PK-C), which phosphorylates proteins (allosteric mod)
5. IP3 causes release of Ca+2 from organelles, creating a Ca+2 signal
Agonist
Chemical messenger that binds to a receptor and triggers a cell’s response
Antagonist
Molecule that competes w/ another for a receptor and binds to the receptor but does not trigger a cellular response
aka: anti-histamine?
Epinephrine can bind to different isoforms of the adrenergic receptor…
Target response depends on the target receptor
- diff receptor = diff results
Signal termination
- After the cell’s response has been initiated, the 1st messenger must be stopped.
- After the cell’s response has been initiated the 2nd messenger must also be removed.
Many diseases & drugs have their effects at the?
Receptor or signal transduction step
Signal termination: 1st messengers can be…
- Degraded by extracellular enzymes (outside cell)
—–ex: ACHE, MAO - Endocytosis of receptor-ligand complex (inside cell)
Signal termination: 2nd messengers can be…
- Degradation of the 2nd messenger
- Pumping of ions out of the cytoplasm (put it back into its rightful organelle)
