11.08.11+-+Cell+Polarity+&+Junctions

Cell Polarity & Junctions


 * Type || Participants || Protein || Filament || Type of Protein Interaction || Function || Features ||
 * Zonula Ocludens (Tight Junction) || Cell-Cell || Claudin || N/A || Homophilic || Barrier, Fence || band of branching strands; number of strands is proportional to degree of impermeability ||
 * Zonula Adherens (Adherens Junction) || Cell-Cell || Cadherin || Actin || Homophilic || Barrier, Adhesion || Actin affiliated within cell via catenin proteins; requires Ca2+ to be functional ||
 * Macula Adherens (Desmosomes) || Cell-Cell || (Different) Cadherins || Intermediate Filaments || Homophilic || Adhesion, cellular structure || Intermediate filament (keratin) anchored via cytoplasmic anchor proteins ||
 * Gap Junction || Cell-Cell || Connexons || N/A || Homo/Heterophilic || Intercellular communication/coordination || 6 connexins come together to form a connexon which lines up with a connexon on another cell ||
 * Hemidesmosomes || Cell-ECM || Integrins || Intermediate Filaments || Heterophilic || Adhesion || Intermediate filament anchored to ECM via integrins in plasma membrane extending into basal membrane ||
 * Focal Adhesions || Cell-ECM || Integrins || Actin || Heterophilic || Adhesion || Actin anchored to ECM via integrins ||
 * Selectins || Cell-Cell || Selectins || None || Heterophilic || Cell migration || Active in cell migration by binding to membrane bound carbohydrates; Ca2+ dependent ||


 * 1. Describe the function and tissue distribution of gap junctions and what regulates the passage of molecules through these junctions.**

There are many different types of gap junction proteins, called Connexins. For the most part, 6 connexins circle to form a hexagon called a connexon. Some connexins form heteromeric connexons, others form homomeric connexons. Connexins are broken down rapidly; they have a half-life of 1.5 hours. The diameter of the gap junction created by a connexon is about 1.5 nm. They allow the passage of molecules like glucose and ATP, but RNA/DNA/proteins will not pass.

Gap junctions provide a method of direct communication between neighboring cells via holes in their plasma membranes. They couple two or more cells' metabolism and electrical charge. Gap junctions are important in the function of the heart (action potentials pass between cardiac muscle cells via gap junctions), electrical synapses, the retina, and the metabolism of the bone (cells in bone must get nutrients via gap junctions because they are non-vascularized). If a gap junction connected cell (e.g. cardiac muscle) undergoes apoptosis, messaging to other cells passes through gap junctions.

Control of the opening and closing of gap junctions is via second messengers. They are very heavily regulated by dopamine, which can decrease the permeability of gap junctions between neurons by increasing cAMP levels.

Gap junctions closely associate cellular membranes; when many gap junctions aggregate, large areas of cellular membrane become closely involved. Disorders of gap junctions can cause blindness, deafness, and heart arrhythmias.


 * 2. Describe the types of adhesions formed between cells and the function of these adhesions.**
 * 3. Describe the type of adhesions formed between cells and the ECM and the functions of these adhesions.**
 * 4. What structures connect the cytoskeletal system to the plasma membrane?**

We're covering 4 types of cell-cell junctions:

Zonula Ocludens or Tight Junctions: The Latin name for tight junctions is zonula ocludens which is actually pretty helpful to remember their location and function. Zonula means that the junction completely encircles the cell and occludens means to occlude, or close off the space between the cells. They are the most apical of the junctions between epithelial cells (they are actually only present in epithelial tissues). As their name implies they function is as a barrier between sides termed the apical and the baso-lateral side; they also have a separate functions as a fence, which means membrane proteins are not allowed to pass them from bass-lateral to apical or the other way. The apical side is toward the lumen and the baso-lateral side is toward the body/rest of the tissue.

The impermeability of the barrier function of the tight junction is proportional with the number of claudin adhesions present in the epithelium. Claudin is a transmembrane protein in epithelial cells that interacts homophilically with claudin in adjacent cells. The junction is formed by a band of branching strands, the more branches (bladder vs. proximal renal tubule) the more impermeable.

Zonula Adherens or Adherens Junctions: The Latin name is again helpful: zonula (encircling) adherents (adhesion). This junction is just baso-lateral to the zonula ocludens. These homophilic junctions are formed by plasmembrane proteins called cadherins that are anchored via proteins called catenins to actin networks within the cell. They are Ca2+ dependent to function.

Gap Junctions Really a conglomeration of many little pores called connexons which are formed from six connexins arranged in a circle. The connexon on one cell lines up with a connexon on another cell and the pore opens up between them. Gap junctions can be large with many connexons in the same region or small with only few connexons. Connexons are 1.5 nm in diameter and small molecules (cAMP) transduce easily.

Macula Adherens or Desmosomes Again, the Latin is helpful. Macula means spot and adherens means adhesion. It is exactly that, a spot adhesion. Bonus fact: desmo means bond or fastening and soma means body in Greek. Its components are a class of membrane proteins called cadherins (non related to the zonula adheren cadherins; e.g. desmoglein and desmocollin), cytoplasmic anchor proteins (plakoglobin and desmoplakin), and intermediate filaments (keratin in epithelial cells).

And 2 types of cell-extra-cellular junctions

Hemidesmosomes Like desmosomes, because they are associated with intermediate filaments in the cytosol, but different because they are between epithelial cells and the subjacent basal lamina and their membrane proteins are called integrins (not cadherins).

Focal Adhesions Like hemidesmosomes because they use integrins, but affiliated with actin within the cell


 * 5. What structure functions as both a barrier and a fence?**

Turns out that this is an important distinction. The zonula ocludens functions as both a barrier and a fence.

To keep them distinct in my mind I think of barriers as being only above ground (in the extracellular space) while fences have poles that extend into the ground (plasma membrane). The barrier function is the action of blocking paracellular communication (i.e. extracellular fluid is trapped on one side or the other). The fence function is the action of blocking the migration of intramembranous proteins (i.e. maintain cell polarity by creating two distinct membrane halves).


 * Type || Participants || Protein || Filament || Type of Protein Interaction || Function || Features ||
 * Zonula Ocludens (Tight Junction) || Cell-Cell || Claudin || N/A || Homophilic || Barrier, Fence || band of branching strands; number of strands is proportional to degree of impermeability ||
 * Zonula Adherens (Adherens Junction) || Cell-Cell || Cadherin || Actin || Homophilic || Barrier, Adhesion || Actin affiliated within cell via catenin proteins; requires Ca2+ to be functional ||
 * Macula Adherens (Desmosomes) || Cell-Cell || (Different) Cadherins || Intermediate Filaments || Heterophilic || Adhesion, cellular structure || Intermediate filament (keratin) anchored via cytoplasmic anchor proteins ||
 * Gap Junction || Cell-Cell || Connexons || N/A || Homo/Heterophilic || Intercellular communication/coordination || 6 connexins come together to form a connexon which lines up with a connexon on another cell ||
 * Hemidesmosomes || Cell-ECM || Integrins || Intermediate Filaments || Heterophilic || Adhesion || Intermediate filament anchored to ECM via integrins in plasma membrane extending into basal membrane ||
 * Focal Adhesions || Cell-ECM || Integrins || Actin || Heterophilic || Adhesion || Actin anchored to ECM via integrins ||
 * Selectins || Cell-Cell || Selectins || None || Heterophilic || Cell migration || Active in cell migration by binding to membrane bound carbohydrates; Ca2+ dependent ||