Lecture 16: Cell Junctions

Epithelia

• sheets of tightly bound cells found within epithelial tissues

  • epithelial tissues being those which line the gut, or the epidermal covering of the skin

Apical-basal Polarity

• results from the differential distribution of phospholipids, protein complexes, and cytoskeletal components

• established by epithelial cells

Cell Junctions

• connect cells at the lateral region within the epithelium

• where cytoskeletal filaments are anchored, and transmit stresses across the interiors of the cells

• 3 different types:

  • tight junctions

  • adherens junctions

  • gap junctions

Adherens Junctions

• associate with the actin cytoskeleton via cadherin/catenin complex

Cadherins

• meaning calcium adherin

• homophilic transmembrane protein

  • cadherin-cadherin same type homophilic binding is Ca²⁺ dependent

  • Ca²⁺ removal means the junctions fall apart

• catenins link cadherins to the actin cytoskeleton

• may be typical (homophilic), or atypical (heterophilic)

Cadherin Domain

• each cadherin domain forms a rigid unit, joined to the next cadherin domain by a hinge

• Ca²⁺ ions bind to each hinge and prevent it from flexing

  • cadherin-cadherin binding is Ca²⁺ dependent

• when Ca²⁺ is removed, the hinges flex, and the structure becomes floppy

  • Ca²⁺ removal means the junction falls apart

Cadherin Examples

• E-cadherins: epithelial

• N-cadherins: neuronal

Typical Cadherin

• homophilic

  • cadherin binds with same type cadherins

• cadherins mediate highly selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells

  • cells are sorted by the type/amount of cadherins

Atypical Cadherin

• heterophilic

• cadherin binds with different types of cadherin

• example:

  • cells with Fat (Ft) bind cells with Dachsous (Ds)

Catenins

• link classical cadherins to the actin cytoskeleton

Planar Cell Polarity

• collective allignment of cell polarity across the tissue plane

Tight Junctions

• the selectively permeable epithelia barrier requires that the adjacent cells be sealed together by tight junctions, so that molecules cannot leak freely across the cell sheet

• visualized via freeze-fracture electron microscopy

• in insects, tight junctions are called septate junctions

Freeze Fracture Electron Microscopy

• method by which tight junctions are visuallized

• seen as a branching network of sealing strands that completely encircles the apical end of each cell

Claudins

• main transmembrane protein forming tight junction strands

  • in assistance with the related occuludin protein

• claudins form selective channels, allowing specific ions to cross the tight-junctional barrier from one extracellular space to another.

Septate Junction

• tight junctions in insects

• organized differently than tight

• also made out of claudins

Gap Junctions

• mediates diffusion between cells between cytoplasms

• clusters of channels that join two cells together

• consist of building blocks of two connexons or hemichannels, one contributed by each of the communicating cells

  • each connexon is formed of a complex of 6 connexin proteins

• pore sizes small enough to allow for the exchange of inorganic ions and small molecules, but not macromolecules.

Connexin

• complex of 6 connexin proteins form a connexon, which when contributed with connexon from another communicating cell builds vertebrate gap junctions

• innexins are the invertebrate equivalent