anat7.txt

Cell Junctions

• 1.  Anchoring junctions - mechanically attach cells to other cells or the ECM
• 2.  Occluding junctions - seal the contacts between cells
• 3.  Channel-forming/communicating junctions - allow chemical or electrical signals to pass from one cell to another.

• 1.  Transmembrane adhesion protein - spans the cell membrane and connects the inside and outside environment of the cell
• 2.  Adaptor protein - allows recruitment of additional components to the adhesion complex and regulates the adhesion complex
• 3.  Cytoskeletal linkers - physical link between the adhesion complex and the cytoskeleton

Classified by the number of times they cross the membrane ie. single pass, two pass, three pass, etc.

• 1.  Tight Junctions (Occluding Junctions)
• 2.  Zonula Adherens aka adherens junctions (Anchoring Junctions)
• 3.  Desmosomes (Anchoring Junctions)
• 4.  Gap junctions (Channel-forming Junctions)

• made up of large protein complexes
• 'Clustering' of the transmembrane adhesion proteins in the plasmamembrane - the combined strength of multiple bond interactions increases overall strength of the junction
• The clustered adhesion proteins link to cytoskeletal network which produces a huge tension-bearing protein interaction network running through the tissue

• A technique used to look at membranes that reveal the pattern of integral membrane proteins.
• Casts are made of frozen membrane surfaces

• zonula= a belt that goes all around the cell
• located very near the apical domain; join neighboring cells closely

• Formed by strands of interacting transmembrane proteins observable by freeze-fracture electron microscopy.
• Specifically, tight junctions are formed by the transmembrane adhesion proteins Claudin and Occludin binding to the same type of molecule on neighbouring cells (i.e. ClaudinClaudin or Occludin-Occludin interactions).

Controls solute diffusion between cells (lateral diffusion)

• 4 pass transmembrane protein
• essential for tight junction formation

• 4 pass transmembrane receptor
• required for barrier function
• not needed for maintaining overall tight junction structure

Barrier permeability can be tested by using a dye/tracer that is added to either the apical or basal side of the epithelium and observing whether the dye/tracer diffuses over the junction

Loss of tight junction claudin 16 disrupts clearing of electrolytes from blood- leads to calcified deposits in the kidney and kidney failure.

• Form a continuous adhesion belts that completely cover the circumference of the cell on the lateral domain just basal to tight junctions
• Critical in epithelia for the formation of 2D sheets of cells
• Composed of single pass transmembrane proteins called classical cadherins
• link to the actin cytoskeleton

• 1. Calcium binding to cadherin causes cadherin's extracellular domain to straighten and form "cis-homodimers" on the same cell.
• 2. Cadherin straightening promotes "trans" homodimerization, which means that a cadherin cis-homodimer on one cell binds another cadherin cis-homodimer located on the surface of another cell.
• 3. This trans-bound complexes cluster together in the plane of the membrane
• Cadherins link to the actin cytoskeleton via intracellular anchoring complex containing adapter proteins called "catenins".

Loss of cadherin causes some cancers.  Loss of classical cadherin is associated with loss of epithelial structure which is a hallmark of cancer.

• based on adhesion between cadherin-like receptors: Dsc  (Desmocollin) and Dsg (Desmoglein)
• Bind the keratin family of intermediate filaments
• small spotlike-junctions that form along the entire lateral domain of cell types in tissues that are exposed to tensile forces/mechanical stress like skin
• maintan the orientation of cytoskeletal elements between cells

loss of Dsg cause Pemphigus vulgaris- loss of adhesion between layers of the skin results in skin blistering

• allow communication and sharing of nutrients between cells
• important in both epithelial and non-epithelial cells ie. cardiac myocytes
• also involved in hearing

Connexin are the gap junction adhesion proteins. Six connexin form a hexamer called a connexon in the lateral membrane domain of one cell membrane. A connexon will then bind a similar hexamer/connexon in the lateral membrane domain of a neighbouring cell to form a functional channel that can be regulated (ie. can be opened or closed) and can pass small molecules between linked cells in the epithelium

Loss of connexin 26 causes Vohwinkel syndrome (keratodema)