Lecture 3 Block 2 Flashcards
(40 cards)
What are the two distinct membrane domains to the plasma membrane?
The apical side and the basolateral side
What is the basolateral side of the plasma membrane?
The basolateral side of an epithelium always sits on an extracellular matrix secreted by the epithelial cells (called the basal lamina) that faces the ‘blood side’ of the cell layer and is directly exposed to the ‘interstitial fluid.’
What is the apical side of the plasma membrane?
This is the side that is exposed to the ‘outside’ of the body (b/c technically the lumen of the intestine is topographically outside the body) - an exception is the choroid plexus that has the apical surface exposed to CSF which is an internal environment
What are the principal ‘barrier epithelia?’
Cell layers that line organs that have large surfaces exposed to the exterior of the body and include:
- GI Tract
- Kidney (renal) nephron
- Liver
What are the other significant epithelial cell layers (not including the GI tract, Kidney nephron, and liver)?
Choroid plexus
Retina
Exocrine glands (collectively)
What are the two pathways available for material flow between compartments separated by epithelium (this flow represents transendothelial transport)?
- Paracellular
- Transcellular
What is paracellular transport?
That which occurs between adjacent cells
What is transcellular transport?
Across individual cells - involves sequential flux across basolateral and apical membranes.
What does flow through the paracellular pathway require?
Tight junctions
Four things about tight junctions?
- Serve as barrier reduce free diffusive movement
- Provides barrier to prevent intermixing of molecules
- Generally located near the apical pore of epithelial cells
- Permselective
How do tight junctions prevent free diffusive movement?
Tight junctions reduce free diffusive movement of molecules via the paracellular pathway due to size inhibition. Molecules that are larger than ~4A struggle to get through due to their size. (Glucose is slightly larger than 4A for example)
How do tight junctions forms a protective barrier to prevent intermixing of molecules?
Tight junction proteins form a chicken wire that separates the lateral (basolateral) and microvilli (apical) domains of the plasma membrane. The tight junctions form a physical barrier (like a fence) that prevents protein movement between the two membrane domains
How is the tight junction permselective?
The claudin family of proteins plays a critical role in establishing this permselective character of tight junctions. The claudin complex forms aqueous pores with different amino acid combinations (leading to different charged characteristics of each pore) allowing for movement of different molecules.
What do claudins that form pores that contain a surplus of cationic residues in the postulated pore forming region favor transporting?
Favor the paracellular movement of anions (like Cl-)
What do the homologous regions of claudins that contain a surplus of anionic residues favor transporting?
Favor the paracellular flux of cations (like Na+)
What are secretagogues?
Endocrine signal molecules that stimulate release of zymogens from the acinar cells in the lumen of the acinus
What are four secretagogues?
CCK - Cholecystokinin
ACh - Acetylcholine
VIP - Vasoactive Intestinal Peptide
Secretin
What are the most important secretagogues and how do they work?
CCK and ACh are the most important secretagogues for stimulation of zymogen secretion.
They work by binding to the G protein-coupled CCK receptor, or the muscarininc ACh receptor, and activate PKC (protein kinase C) and producing an associated rise in intracellular Ca2+.
How do VIP and Secretin stimulate zymogen secretion?
Through activation of PKA (Protein Kinase A) via interaction with distinct GPCRs
What is the general mechanism of zymogen granule release - Stimulus-Secretion Coupling (SSC)?
SSC is a process associated with exocytosis using the major proteins: SNARE proteins, Rab proteins, and Synaptotagmin proteins
What are SNARE proteins?
(Soluble NSF Attachment Protein Receptor) snap proteins play a critical role in releasing the SNARE complex after the fusion event. There are v-SNAREs (vesicle-SNAREs) and t-snares (target-SNAREs) and they assist in getting the right vesicles to fuse in the right place
What are Rab proteins?
Small G-proteins (that bind and hydrolyze GTP) that serve as molecular switches to help assemble the SNARE fusion complex and aid in targeting specificity.
What are Synaptotagmins?
They are integral membrane proteins in vesicle membranes. They bind Ca2+ and play a key role in stimulating the fusion event in exocytosis.
What is the key concept regarding the general strategy of SSC?
It is energetically unfavorable for vesicle membranes and plasma membranes to get close to each other as they both tend to have net negative surface charges and repel each other. The SNAREs (regulated by Rab and augmented by Synaptotamins) couple vesicles to the cytoplasmic face of the plasma membrane and draw the vesicles close to the membrane. This facilitates fusion of vesicle membrane with plasma membrane - without this functional SNARE the efficiency of vesicle fusion is greatly decreased
