JUNCTIONS AND JUNCTIONAL COMPLEXES
Cell junctions consist of protein complexes and provide contact between neighboring cells, between a cell and the extracellular matrix. Human cells (and most vertebrate cells in general) have tight junctions, adherens junctions (zonula/fascia) and gap junctions. The molecules responsible for creating cell junctions include various cell adhesion molecules.
ZONULA OCCLUDENS ("tight junctions"): closely associated areas of two cells whose membranes join together forming a virtual impermeable barrier to fluid. Composed of a branching network of sealing strands, each strand acting independently from the others. Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes
Although more proteins are present, the major types are the claudins and the occludins. These associate with different peripheral membrane proteins located on the intracellular side of plasma membrane which anchor the strands to the actin cytoskeleton. Thus, tight junctions join together the cytoskeletons of adjacent cells.
- Hold cells together.
- Block the movement of integral membrane proteins between the apical and basolateral surfaces of the cell (allowing the specialized functions of each end of the cell).
- Prevent the passage of molecules and ions through the space between cells.
Function: Adherens junctions may serve as a regulatory module to maintain the actin contractile ring.
MACULA ADHERENS (desmosomes and hemi-desmosomes; "spot junctions"): spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Molecular complexes of cell adhesion proteins (e.g., desmosome, desmoglein and desmocollin = cadherin protein family) and linking proteins that attach the cell surface adhesion proteins to intracellular keratin (cytokeratin) or desmin filaments.
Function: They help to resist shearing forces and are found in simple and stratified squamous epithelium. Desmosomes are also found in muscle tissue where they bind muscles cells to one another.
Blistering (bullous) diseases: If the desmosomes connecting adjacent epithelial cells of the skin are not functioning correctly, layers of the skin can pull apart and allow abnormal movements of fluid within the skin, resulting in blisters and other tissue damage. Blistering diseases such as pemphigus vulgaris can be due to genetic defects in desmosomal proteins or due to an autoimmune response. These patients are often found to have antibodies that bind to the desmosomal cadherins and disrupt the desmosomes.
Gap Junctions (nexus): protein complex (connexon) forming a transmembrane hemipore connected to a connexon (second, associated hemipore) in an adjacent cell. Provides a continuous channel between the two cells. At a gap junction, the intercellular space narrows from 25nm to 3nm and unit connexons (hemipores) in the membrane of each cell are attached to connexons (hemipores) another.
Function: Ion transport; cell-to-cell communication; synchronization of cellular activity within a tissue (e.g., cardiac muscle, pancreatic islets, etc.) Gap junctions between skin keratinocytes function in synchronizing proliferation and differentiation. Most astrocyte populations and some neuron populations in the CNS are interconnected by gap junctions, again to synchronize their activity(ies).
An intercalated disc is an undulating double membrane separating adjacent cells in cardiac muscle fibers. Intercalated discs support synchronized contraction of cardiac tissue.
An intercalated disk is comprised of three types of membrane junctions:
- Fascia adherens are anchoring sites for actin, and connects to the closest sarcomere.
- Macula adherens stop separation during contraction by binding intermediate filaments joining the cells together also called a desmosome.
- Gap junctions allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle.
SUMMARY COMPARISON OF JUNCTIONAL COMPLEXES
Epithelium (attaches to)
GI EPI- Zonula occludens (none/actin?), zonula occludens (actin), macula adherens (cytokeratin)
Cardiac myocytes- fascia adherens (actin thin filaments), macula adherens (desmin) also has gap junctions