- author "JLeezy"
- tags "PSL"
- description "Lectures 4-8"
- fileName "Epithelial Cells"
- freezingBlueDBID -1.0
- Epithelial Cells
- Transport and secretory cells
Two sections of epithelial cells
- Apical: flat side that interacts with lumen
- Basolateral: rest of the cell's surface, interacts with blood/ECF
Trans- vs. Paracellular
Transcellular is through cells, paracellular is between them (via tight junctions).
How do the kidneys reabsorb nutrients?
- Nutrients begin in lumen
- Na+/K+ pumps create Na+ concentration gradient (Na+ goes out of cells)
- Na+ gradient powers active transport of nutrients into cells via apical side
- Nutrients exit cells via passive carrier proteins on basal side
Symptoms of CF
Thick mucus secretions and salty sweat.
Three hypotheses of how CF causes lung infections
- 1: A large decrease in Cl- absorption (mutant CFTR) --> increase in NaCl concentration on airway surfaces --> impedes natural antibiotics, leading to more infections
- 2: A large increase in Na+ absorption (no CFTR, no ENaC inhibition) --> water follows solute --> low airway surfaces liquid volume --> more infections
- 3: No CFTR-mediated HCO3- transport --> without HCO3- being secreted into the airways, pH gets too acidic (?) or causes a lack of defensins (?) --> more infections
Anion (Cl-) channel. Mutated in CF. Inhibits ENaC channel when working properly.
Exocrine vs. endocrine secretion
- Exocrine: secretion into lumen
- Endocrine: secretion into bloodstream (long-range)
Secretory gland for saliva
How does secretion work?
Cl- enters cell via basolateral side and exits via apical side (into lumen); water follows solute.
Cellular path of proteins that are destined for secretion
These proteins are made on the rough ER, sent to the Golgi, then the plasma membrane.
Pulse-Chase experiments (and results)
- Add labeled amino acids to pancreatic cells for only three minutes to see where proteins that were synthesized during those three minutes go.
- 3 min: rough ER
- 10 min: Golgi
- 30 min: ready for secretion @ membrane
Pores that trap growing polypeptides halfway across the lipid bilayer. Periodically open during the protein's growth to give it a chance to stay in cytosol or head to the membrane.
Cover vesicles and help with curvature AKA formation of the vesicles.
SNARES (2 types)
- Proteins that assist with vesicle fusion.
- v-SNARES: In the Vesicle, bind to t-SNARES
- t-SNARES: Extend from vesicle's Target location
Endocrine vs. paracrine agents
- Endocrine agents, AKA hormones, transmit signals over long distances
- Paracrine agents affect nearby cells
Dissociation equation (a smaller Kd means. . ?)
- Smaller Kd means more sensitive signal reception.
Agonist vs. antagonist
- Agonists are ligands that are activators
- Antagonists are ligands that are inhibitors
Na+ (and some Ca++) channel that requires two Ach molecules to bind for it to open. Nicotine can do the function of Ach.
GPCR: cAMP Pathway
Ligand binds GPCR --> activates G-protein --> β and γ subunits head off to open a K+ channel and inhibit some Ca++ channels --> α subunit activates/inhibits adenylyl cyclase --> adenylyl cyclase increases/decreases cAMP levels --> 4 cAMP molecules activate PKA complex
GPCR: Ca++ Pathway
Ligand binds GPCR --> activates G-protein --> β and γ subunits head off to open a K+ channel and inhibit some Ca++ channels --> α subunit activates PLC --> PLC hydrolyzes (splits) PIP2 into IP3 and DAG --> IP3 releases Ca++ from the ER, DAG activates PKC
Protein that requires 4 Ca++ molecules to bind. Once activated, calmodulin can binds to and activate other proteins.
Methods of GPCR regulation (@ receptor, G-protein, and second messengers)
- Receptor: desensitization, down regulation
- G-protein: GTPase, lipid modification
- Second messengers: elimination of second messengers from cell
Norepinephrine binds β-receptor --> G-protein, adenylyl cyclase, cAMP, PKA --> PKA phosphorylates SNARES, causing them to fuse and secrete their proteins
How does salivation work?
IP3 releases Ca++ from the ER. This Ca++ activates Cl- channels and transporters, allowing Cl- to leave the cell. Water follows solute - voila! Salivation!
What causes Cholera?
Constant activation of G-proteins (and thus adenylyl cyclase --> cAMP --> PKA), and PKA keeps CFTR activated.
Nuclear Receptor Superfamily
Large class of intracellular receptors that control hormones and nutrients as signals. Each has three sections: activation, DNA binding, and ligand binding.
- A simple (just has an α subunit) G-protein that activates MAP kinase.
- *Some cancers are caused by a mutated Ras that results in continual activation.
Regulates the entire cell cycle.
Receptor Tyrosine kinases
- Once activated (ligands bind) they dimerize, and then activate Ras with the classic GDP --> GTP.
- *No second messengers in this pathway.