Lectures 5 & 6 Outline Flashcards
What are the 4 mechanisms for cell to cell communication?
- Gap junction dependent communication
- Contact dependent signaling
- Local signaling
- Long distance communication (secreted signal)
What does long distance communication (secreted signal) involve?
- hormones
- neurotransmitters
- neurohormones
What are the 2 main categories based on receptor location?
- Intracellular receptors/lipophilic signals
2. Cell membrane receptors/lipophobic signals
Intracellular receptors
ligands are usually lipophilic (=hydrophobic)
- steroid hormones for ex
the signal is:
- able to diffuse through cell membrane & bind to receptors IN the nucleus or cytosol
often alter gene expression (slow but long-lasting)
Cell membrane receptors & membrane bound organellses/lipophobic signals
ligands are usually lipophobic (=hydrophilic)
- insulin & other peptide hormones for ex
ligand does NOT diffuse through cell membrane
bind to membrane receptors
cause intracellular cascade
What are the 4 intracellular signal pathway cell membrane receptors?
- Integrin receptors
- Receptor channels
- Receptor enzyme
- G-protein coupled receptor (GPCR)
G-protein coupled receptors (GPCRs) description
activation of GPCR leads to generation/release of second messengers
- a second messenger is a signaling molecule synthesized or released by a cell in response to an extracellular signaling molecule (hormone, for ex)
- sometimes they are synthesized, sometimes they are released from a storage compartment
- small, diffusible (can be hydrophobic, hydrophilic, or a gas)
- stimulate a biological response
G-protein coupled receptors (GPCRs) properties
hundreds of known GPCR
- may have unknown function (orphan receptors)
GPCRs also called
- metabotropic receptors
- 7 transmembrane domain receptors (7TR)
- serpentine receptor
activation of GPCR leads to generation/release of second messengers!
What are the 3 specific G-protein coupled receptors (GPCRs) examples?
- adenylyl cyclase
- phospholipase-C
- phospholipase A2
G-protein coupled receptors (GPCRs): Andenylyl cyclase example
- ligand binds to G protein receptor
- activates the G protein (3 subunits, alpha, beta, gamma)
- once activated, the G-protein can diffuse along the inside leaf of the membrane (lipid-anchored protein)
- the activated receptor can stimulate several G-proteins - G-protein diffuses along the inside of the membrane to activate the amplifier enzyme ADENYLYL CYCLASE
- each G-protein activates one AC - Adenylyl cyclase converts several hundred ATP into cAMP
- cAMP is the 2nd messenger
- cAMP can diffuse throughout the cell - cAMP activates PROTEIN KINASE A (PKA)
- PKA diffuses within cell to phosphorylate many other proteins
- many types of proteins can be phosphorylated, giving rise to complex cellular responses
G-protein coupled receptors (GPCRs): Phospholipase-C example
- Ligand binds to & activates G protein receptor
- G-protein activates the Phospholipase-C (the amplifier enzyme)
- PLC degrades membrane phospholipids into TWO 2nd messengers:
(1) Diacylglycerol & (2) Inositol tri-phosphate
- DAG stays associated with the lipid (it’s a diglyceride)
- IP3 is a small polar molecule that diffuses throughout the cytoplasm - DAG activates protein kinase C (=PKC)
- PKC diffuses within the cell, & phosphorylates other proteins - IP3 binds to the IP3 receptor on the endoplasmic reticulum
- activates IP3 receptor, allows stores of Ca2+ to be released into the cytoplasm
- this Ca2+ becomes another 2nd messenger
What are the “classic” second messengers?
- cAMP, cGMP
- IP3, DAG
What are the “novel” second messengers?
- Ca2+
- gasses
- lipids
- endocannabanoids
G-protein coupled receptors (GPCRs): Phospholipase A2
- the Arachidonic Acid pathway is similar to the PL-C pathway
- G-proteins activate Phospholipase A2 (amplifier enzyme)
- PLA2 degrades phospholipids into Arachidonic Acid
- Arachadonic acid (& its eicosanoid metabolites) have a dual function:
1. Are themselves 2nd messengers within a cell
2. Diffuse out of the cell & act as a ligand for GPCR cell membrane & adjacent cells
What is the specificity & modification of signaling pathways?
- for years physiologists were not able to explain why the hormone epinephrine (adrenaline) caused some blood vessels to constrict & others to dilate
- the presence of RECEPTOR ISOFORMS is the reason
some ligands can activate multiple receptors
- epinephrine activates alpha & beta2 receptors
some receptors are PROMISCUOUS (activated by more than 1 ligand)
- alpha receptors may be activated by either epinephrine or norepinephrine
- beta2 receptors may be activated by either epinephrine or norepinephrine
