Session 6: Cell Adhesion Flashcards
Describe the 3 major junction types and their role in tissue architecture.
T - tight junctions - compartment separation
A - anchoring junctions - modifiable tissue integrity
G - gap junctions - cell-cell modification
What is the importance of cell-cell and cell-substrate interactions?
They hold together tissues
List the 3 components of a junction
- cell membrane
- transmembrane proteins
- +/- cytoskeletal proteins
What is a junctional complex?
different junctions co-localize and may include links to cytoskeletal proteins to increase mechanical integrity
Why types of junctions are involved with the blood brain barrier?
- (TG) tight junctions restrict passage
- (AJ) adherens junctions stabilize cell-cell interactions
consequence: restricts passage and is dependent on lipid solubility and MW (< 400MW)
What is the challenge with drug delivery through the BBB? What is done about it?
Many drugs are too big or too hydrophilic to cross the BBB
Mannitol - used to shrink the endothelial cells of the BBB and increase permeability (transient opening of the TJ)
- disadvantage of mannitol –> toxicity
Cereport - create transient opening (15 mins) and release of the drug at the same time
What damage is done to the BBB post stroke?
There is junctional protein degradation that leads to brain edema (swelling)
- fluid leaks from the vessels to tissue with less restriction
Where are tight junctions and what do they do?
Location: between epithelial or blood vessel endothelial cells (separate in vs. out)
- acts like band that rubber bands two cell membranes together
- stops lateral diffusion in cell membrane
- prevents porter proteins from diffusing past the TJs
Explain the effect of helicobater pylori on tight junctions.
Bacterial protein associates with TJs and alters their composition/function
- disrupts barrier
- cells that were protected, now exposed to acid
- rapid growth to heal lesion may lead to DNA replication errors and gastric carcinoma
Describe the structure of anchoring junctions.
Composed of two parts:
integrin - transmembrane proteins
cytoskeleton - intracellular proteins (NOT MICROTUBULES)
What are the two classes of anchoring junctions?
adherens junctions
- microfilament (actin) and integrin
desmosome junctions
- intermediate filament and integrin (holds skin cells together)
What is the function of integrins and how are they regulated?
function: cell-cell and cell-matrix interactions
- blood clotting
- cell migration (good and bad)
regulation: increase phosphorylation of cytoplamic tail
- cell retraction during movement
- WBC infiltration
- metastasis
Explain how integrins and WBCs interact to heal a wound.
- WBCs roll along the surface of the cell
- WBCs stick to the wall of wounded tissue inside the blood vessel
- integrins interact w/ proteins on endothelial cell surface (haptotactic molecules on lumen side)
- rolling stops and integrin on WBC transfers signal to endothelial cell
- activates cytoskeleton protrusion of WBC
- WBC begins to migrate across blood vessel wall and into wound
Explain the case study of adherens junction not functioning properly: focal segmental glomerulosclerosis (FSGS).
- kidney adherens junctions poorly formed (integrin and microfilaments) and poorly interact w/ ECM –> leaking protein (albumin)
- excess suPAR constantly disrupts integrin and slit diaphragm (filtration of kidney) fails –> leaks proteins into urine
Describe gap junctions and their function.
- FAST cell-cell communication
- connexin proteins make channels to join cytoplasm of adjacent cells
- high Ca2+ or H+ = closed channels
- low Ca2+ or H+ = open channels (<1000MW)
