Cell Adhesion

junction components

cell membrane + transmembrane proteins + pos/neg cytoskeletal proteins

Name the three junction types:

• Tight junctions

• Anchoring junctions

• Gap or communicating junctions

junctional complexes

co-localized junctions, may include links to cytoskeletal proteins to increase mechanical integrity (i.e. tight junctions + adhesion belt + desmosome)

blood brain barrier (BBB)

junctions between cerebral microvascular endothelial cells

• tight junctions restrict passage

• anchoring junctions stabilize cell-cell interactions

• limited compounds can cross junctions (<400 MW and/or lipid soluble)

Explain therapy concepts for crossing the BBB:

• cell modification: hyperosmotic infusion w/ mannitol → endothelial cell shrinkage → temporary opening of BBB → increased permeability

• drug modification: increase drug lipophilicity → increases BBB penetration for treating brain cancer

tight junctions

between epithelial or blood vessel endothelial cells

• separates “in” vs “out”

• stops lateral diffusion in membrane

• strands of tight junction occludin & claudin proteins create a seal

anchoring junctions

generally composed of two parts

• integrin: transmembrane proteins

• cytoskeleton: intracellular proteins

has two classes: adherens and desmosome junctions

• adherens: microfilament + integrin

• desmosome: intermediate filament + integrin

integrins

transmembrane proteins that provide physical and functional links between interior and exterior of cell; has alpha and beta dimers

How is integrin function regulated?

• increased phosphorylation of cyto tail via integrin release of ECM protein cell

• increased migration over/through extracellular matrix via WBC infiltration

• increased cancer cell spread through ECM via metastasis

gap junctions

enables fast cell-to-cell communication via channels made by connexin proteins that join the cytoplasm of adjacent cells

• maintains 2-4 nm separation

• controls channel opening (high Ca²⁺⁺ or high H⁺ = closed and vice versa)