Cell Junctions Flashcards
What is the order of cell junctions from apex to basal membrane?
tight junction > belt desmosomes > spot desmosomes > hemidesmosomes/focal adhesions
Gap junctions can kind of be anywhere.
Describe Zonula Occludins
and the renal system (disease state)
What would happen if the zonula occludins would not allow anything to pass through?
Serum Mg2+
Urinary calcium
CT scan of kidney
Tight junctions near the apical surface which feature occludins and claudins.
It primarily functions as a seal between the cells but also as a selective barrier.
Occluding and claudins have three domains, a single transmembrane region, a cytoplasmic region that binds to actin, and a extracellular loop that interacts with the neighboring occludin or claudin loop. Loops or small so the association is very tight.
The renal system is meant to filter out blood and produce urine. Filtrate will pass through and 99% will be reuptaked and 1% will become urine.
The tight junctions will selectively allow magnesium and calcium to pass through. (claudins 16 and 19)
Serum: low (produce a lot of urine and magnesium is not reabsorbed into blood)
Urine: calcium high (not reabsorbed)
CT scan of kidney: calcification of kidneys.
Describe zonula adheren
E cadherin
Belt desmosomes;
The protein is cadherin: they feature an extracellular four calcium binding domains, catenins will be the intermediate to binding the actin cytoskeleton, and usually form transhomophilic interaction with neighboring cells (meaning same cells bind to same cells. Without calcium the adhesion would be disrupted.
It associates with the actin belt which contracts
E cadherin is necessary for tight junction formation and cell adhesion to each other and the extracellular matrix. Loss of E-cadherin leads to EMT during cancer progression.
What happens in P-cadherin mutations?
It is expressed in abundance in hair follicles and retinal pigment epithelium.
Victims loose their hair due to lack of association, and their eyes start to degenerate leading to blindness.
Describe macula adherins
Spot desmosomes are primarily for adhering cells to one another. They also display cadherins known as desmocollins and desmogleins.
ON the cytoplasmic surface they form plaques containing desmoplakin, plakoglobin and plakophilin. THese plaques bind intermediate filaments.
They appear as ladders on the slide.
Like belt desmosomes, they feature large extracellular domains.
What are integrins.
Integrins anchor cells to the basement membrane. THey have an alpha and beta subunit. On the extracellular side they bind to the basement membrane and extracellular matrix of fibronectin lamina, collagen etc.
On the intracellular side they primarily bind actin skeleton. (not true to alpha 6 beta 4)
Describe hemidesmosome
They are like half a spot desmosome. They feature integrin alpha-6-beta-4. This bind intermediate filaments.
Describe focal adhesions
their integrins bind to actin filaments. They are critical for growth, cell survival and migration. They also are necessary for the presence of hemidesmosomes.
What happens in pemphigus and pemphigoid?
In pemphigus there is a vesicle forming within the epidermis.
In pemphigoid there is a dissociation between cells of the epidermis and basement membrane.
Both are autoimmune disease.
Pemphigus: Antibodies are attacking desmoglein, the cadherin important in spot desmosomes. So lateral adhesion is compromised.
Pemphigoid: antibodies are attacking hemidesmosomes, breaking between cells and basement membrane.
Describe communicating junctions.
Tightly packed junction with six connexin monomers per half with a hydrophilic channel. They allow the passage of Ca2+ critical for coordinated heart cell contraction.
in the presence of high calcium (a signal for cell death) the channels close to not allow for calcium passage so there is not widespread cell death.
Describe connexin mutations
Connexin 26 is expressed in cochlear hair cells so mutation will prevent transmission of the chemical signal throughout the inner hair cells leading to deafness
Connexin 32 is expressed in peripheral myelin (Shwann cells) which help transmit action potentials so mutations lead to neuropathies.
Describe nonjunctional adhesion mechanism
Leukocyte extravasation during inflammatory response.
involves selectins and IgCAMs.
Selectins: have two calcium binding sites and have a carbohydrate recognition domain.
IgCAMS don’t have calcium binding sites, important are the ICAM and VCAM.
So… when an area is enflamed, selectins will be upregulated. The leukocyte which is circulating the blood stream is slowed down. Selectins are binding to saccharides expressed on the surface of the leukocytes. The endothelium will secrete IL-8 once the leukocyte is slowed down enough. This will activate integrins on the leukocyte which bind to the ICAMs and VCAMS on the endothelium. This is a complete halt, then the leukocyte will migrate inbetween the epithelium and fight the bacteria.
