Zhang - Cell junctions Flashcards
Belt Desmosomes (Zonula Adherens)
Happens right after the tight junctions. Cadherins are responsible for the belt desmosomes to work properly. Has a large extracellular domain with 4 Calcium binding sites. On the intracellular side they have a short cytoplasmic tail that binds to catenins (alpha, beta, and gamma) that attach themselves to the actin cytoskeleton. In order for catherin mediated adhesions to for they have to first form the cis homophylic dimer that allow the catherins to interact with each other on the same cell first. They then form these trans-homophylic dimers so that they can interact with other cells. Belt desmosomes are unique to each type of cell. If this does not work properly then the tight junctions will not be able to form and also the cells will be able to migrate because they aren’t tight down properly. They lose their polarity (dont know which side is apical and which is basilar) and become mesanchymal and can proliferate in other places in the body.
Spot Desmosomes (Macula Adherens)
Like ribbons all over the cell that hold the lateral membrane down.
Integrins
Responsible for hemidesmosomes and focal adhesions. Transmembrane proteins with an alpha and beta subunit. On the extracellular side they bind to the cellular matrix. On the intracellular side they in most cases bind to the cytoskeleton.
Hemidesmosomes
Look like half of a spot desmosomes. Attached to intermediate filaments. Hold the cells to the basement membrane. Integrin-alpha6beta4 is responsible for it.
Focal adhesion
Integrin dependent. It helps anchor to the basement membrane. Attached to actin filaments.
Gap Junctions
A communicating junctions. This allows for one cell to know what is happening in the cell net to it. You need some sort of signal for this to work properly and some sort of transporter to allow the signal to go from cell to cell. The gap junctions are the transporters. Made up of connexons. Six connexIns make up one hexameric connexOn. Gap junctions are group of connexons. Have tiny extracellular loops.
Connexons
Can open and close their “gates”. Think of it as a window that you can open and close when you want. When it is open, calcium can come in when it is closed it cant. Connexons are found in gap junctions to allows signals to flow from cell to cell.
Blistering Diseases
Pemphigus foliaceus - autoimmune disease where antibodies against Desmoglein 1 cause the spot desmosomes to come apart so cells within the epidermis begin to come apart.
Bullous Pemphigoid - causes antibodies to attack BPAG1 so the hemidesmosomes are attacked. So, epithelial cells come apart from the basement membrane.
Mutation in tight junctions
Claudin 16 mutation - autosomal recessive renal disorder, familial hypomagnesemia with hypercalciuria, and nephrocalcinosis.
Diseases of Belt Desmosomes
P-Cadherin mutation - hypertriosis with juvenile macular dystrophy. Progressive degeneration of the central retina. Hair loss
Disease of Gap Junctions
mutations with different connexins associated with deafness.
Selectins
Calcium dependent adhesion proteins. Have extracellular calcium bindding sites. Recognie glycoproteins and glycolipids of other cells. Important for the extravasation process during inflammation.
Ig CAMs
Extravasation molecules. They have Ig like domains
Extravasation Process - Non-junctional process
When you get a cut and bacteria in your blood, there are resident macrophages there to fight it off but you also need the leukocytes. The leukocytes are flying through the blood stream though. So, when you get a cut, p-selectins are upregulated on the endothelial cell surface. This causes adhesions to form between the selectins and the leukocyte cell surface. They essentially act as speed bumps to slow down the leukocytes. Once they get slowed down enough, integrins on the leukocyte cell surface will start to get activated. The leukocytes will then bind to the IgCAMs on the endothelial cell surface. This integrin and IgCAM interaction will cause the leukocyte to come to a complete stop and then they can squeeze themselves into the underlying tissue to fight off bacteria.
Tight Junctions (Zonula Occludens)
Responsible for the apical surface of the cell. You can think of it as a seam running through the cells making them really close to each other. If you think of a room, it would be the part where the ceiling meets the wall.
The proteins that are responsible for the tight junctions are called “occludins” and “claudin”. They are both transmembrane proteins that have extracellular loops that can meet and pull each other very close to each other (JAM1 is another one, but don’t worry about it).
