W3L2 Flashcards
Cell Junction Types
Anchoring Junctions
- Mechanically attach cells to neighboring cells (or ECM)
2 types
- Cell-Matrix
a. Hemidesmosomes (Intermediate filaments)
- One cell binding to something = hemidesmosome
b. Focal Adhesions (Actin)
- Cell-Cell
a. Adherens Junctions (associated with Actin cytoskeleton on intracellular portion)
- i.e. E-Cadherin
b. Desmosomes (Intermediate filaments)
- Cadherin family members with ‘Desmo’ prefix
- e.g., Desmoglein, Desmocollin, etc.
- 2 cells binding to each other = desmosomes
- Fluid can move between cells where there are no desmosomes
Cell-Cell Junction Types: adherens junction and desmosomes
- Adherens junction
- Desmosomes
Adherens junction (associated with actin cytoskeleton) and desmosome (associated with intermediate filament) both fall under the umbrella term of Cadherin Family.
Occluding Junctions (a.k.a. Tight Junctions)
A Cell-Cell Junction
Prevent small molecule passage
- They block things, such as water, solutes, magnesium, calcium, glucose
Commonly found in polarized epithelia
- i.e. small intestine, kidney tubules, blood-brain barrier, etc. Protects self from non-self
- “Leakiness” altered due to tight junction changes allowing or not allowing for paracellular transport
Made up of 2 protein types:
- Claudins, Occludins
Kidney Tubule Tight Junctions
Prevents paracellular transport (transport (BETWEEN 2 cells), like flossing teeth
Zooming in between 2 cells, can see paracellular space between 2 cells.
Depending on the type of tight junction protein (claudin or occludin), it will either allow or not allow solutes and water to go across.
- Claudin2
- Claudin2 is a permissive tight junction protein, allows things like K+ and water to go across.
- Located at proximal tubule - Claudin16
- is a permissive tight junction protein, allows magnesium to cross the paracellular space
- located at ascending limb of loop of henle - Claudin8
- is not permissive tight junction
- located at distal tubule - Claudin4
- is not permissive tight junction
- located at collecting duct
Occludin vs claudin
- occludin is more stringent (strict)
- if you do not express occludin OR if you express occluding but occludin does not arrive at cell surface, then claudin takes over to determine whether things can pass or not
There are 24 diff types of claudin
Communicating Junctions
A cell-to-cell junction type
Channels that mediate passage of ions/solutes or electrical signals from one cell to its partner
Gap Junctions
- Made up of protein called Connexin
Gap Junction structure
6 connexin = 1 connexon on one cell
Connexin is made in ER
Connexon on Cell A bridges to connexon on Cell B. Once the bridge is made, it is called gap junction
Can be open (solutes and water can go across) or closed
Is the most fragile cell-cell junction
Cardiac Myocyte Junction Diseases
These are specialized cell junctions within the intercalated disks and are made of multiple types of junctions: desmosomes, fascia adherens junction, gap junction
- Desmin is a specialized intermediate filament in the heart that makes up desmosome
- you need desmosome and adherens junction in order for gap junctions to stay bound to each other
Purpose of gap junctions in the heart is propagation of electrical signal
- In the heart, activity is faster than nervous transmission aka AP
1 in 10,000 in the population or even 1 in 1000, there is ventricular tachycardia or ventricular fibrillation, causing Arrythmogenic Right Ventricular Cardiomyopathy (ARVC)
- If you need desmosome and adherens junctions in order for gap junctions to stay bound to each other, then anything that disrupts those two things coming together to make a good gap junction is a problem.
Any mutations in the genes that encode the proteins will cause a destabilization of the desmosome or adherens junction, resulting in gap junctions that do not form properly and there are then issues getting the electrical signal from one cell to the other:
- Desmoglein and desmocollin are cadherin proteins in a desmosome
- Can have issues in the cadherin proteins in the desmosome to result in ARVC - Can have issue with N-cadherin, which is part of the fascia adherens junction, resulting in ARVC
- Plakoglobin is associated with the N-cadherin proteins of the fascia adherens junction and is an adaptor molecule that links cadherin to intermediate filaments
– plakoglobin binds to both intermediate filament and actin cytoskeleton - Plakophilin and desmoplakin are adaptor molecules on desmosome
Overall:
- N-cadherin and plakoglobin on adherens junction
- Desmoglein, plakoglobin, desmocollin, plakophillin and desmoplakin are on desmosome
Epidermal Architecture
Stratum corneum
- cutaneous barrier
- dead skin cells
Stratum granulosum
- assembly of cornified envelope (water impermeable layer)
Stratum spinosum
- increase in adhesions
Stratum basale
- regenerative capacity
- polarity complexes
Basement membrane aka basal lamina
- contains integrin
- has stem cells
- made by stratum basale and and fibroblasts of dermis. But bc it is mostly ECM, prof will consider the basement membrane or basal lamina as part of the dermis
Dermis
- there are nuclei of fibroblasts
- is a specialized stroma in the skin
Stroma is extracellular matrix + fibroblasts
Junction
- Adherens junction and gap junctions are everywhere
- Tight junctions not found in lower layers, they are found in the more upper layers
