Cell-Cell Anchoring Junction [2]
Adherens junction connects actin filament bundle in 1 cell with actin filament of next cell
OR
DESMOSOME connects INTERmediate Filaments in 1 cell with IF of the next cell
Briefly describe the 2 BIG types of Tissue environments
Epithelial Tissue= Forms sheets (single or multi) composed of cells bound to extracell matrix via basil lamina and transmit mechanical stress throughout matrix using junctional complexes that attach to cytoskeleton
vs.
Connective Tissue=occupied by extracll matrix proteins (collagen mostly) with fibroblast and chondroblast. This ACTUALLY bears the mechanical physical stress
Occluding/TIGHT Junction
AKA ____ _____
cell TIGHT junction that seals gap between epithelial cells using “Fence” and sealing techniques
AKA (Zonula Occuldens)
Channel-Forming JUnctions
GAP junction that allows passage of small water-soluble molecules from cell to cell
1) What are the 2 different ways a cell may be anchored to the Basal membrane?
2) These both are WHAT TYPE OF JUNCTIONS?
A: HEMIdesmosome anchors cells intermediate filaments to the extracell matrix
and
B: [actin linked cell-matrix adhesion] anchors cells ACTIN filaments to the extracell matrix
2) CELL-MATRIX ANCHORING JUNCTIONS
What are the 4 functional classes of Cell Junctions?
- Anchoring Junctions=cell-to-matrix adhesion and cell-to-cell adhesion
- Occluding Junctions=”TIGHT” sealing Junctions separating apical side from lateral - basal side. Stop things from leaking inbetween cells (ex. BBB/ENDOthelial cells or Intestinal Epithelium)
- Channel-Forming junctions= “GAP” Junctions tht allow small ions and sugars to get inbetween cells
- Signal-Relaying Junctions = complex junctions that uses combination of other junctions
A. What is Paracellular Transport
B. What about “Fence” function
A. Regulated INTENTIONAL Leakage of molecules around or between cells done via “TIGHT” junction adjustment
B. Facilitates Sorting by separating PROTEINS on apical surface from basolateral surface –> creating 2 diff. membrane domains –> dictates how molecules are transported across cell
What is the Tight/Occluding Junction actually made of? [2]
Claudins MAJOR proteins that form Zip-locks on apical aspect of lateral membrane surface of sealed cell
**Occludins help to but are minor
Transcellular Transport
Transporter proteins on diff. sides of the cell utilizing “fence” function to transport/regulate molecules moving thru/across the cell
Explain the types of Anchoring Junctions
Transmit stress from 1 cell to the next cell
- Cell-Cell (Adherens vs. Desmosome)
- Cell-Matrix (Focal adhesion vs. Hemidesmosome)
Describe the Adherens Junction specifically [4]
- Forms adhesive belt just beneath tight junctions
- joins cortical actin bundle in 1 cell to the adjacent cell actin bundle which’ll be connected (by adapter proteins) to –>Cadherin filaments
- Cadherins= Ca+ dependent transmembrane adhesion proteins
-Anchor adapter proteins (catenin family) connect cadherins to actin
Desmosomes
2) What are Plaques?
3) What are “Rivets” ?
- similar to adhereins but links INTERMEDIATE FILAMENT of 1 cell to IF of next cell cytoskeleton instead!
2) looks like “railroad tack” with electron dense “rails” next to each other having intermediate keratin filaments anchored to cytoplasmic PLAQUE
3)PLAQUES attach desmosomal Cadherins (desmogleins and Desmocollins)to Intermediate Keratin Filaments of each cell = “RIVET”
How is Auto-immune dz linked to Desmosomes?
Pt body developes antibodies against desmosomal cadherins leading to blistering and fragile fragile skin and esphogeal problems !
Describe Focal Contacts (AKA Focal Adhesions) [3]
2)What are these important for?
- Links ExtraCell Matrix [ECM] to actin filaments of a cell
- Uses heterodimer Matrix Receptor Integrin to obtain specificity for binding (via beta chain) to actin or intermediate filaments of a cell
- Binds to actin indirectly via anchor proteins
2) [important for fibroblast, migration/movement]
HEMIdesmososme “Half-Desmosome” [2]
- cells link their Intermediate Filaments to the ECM/matrix using anchor adapters which bind to transmembrane integrins–>which integrins bind to ECM matrix integrin (strong adhesion because IF is involved).
- IF of cell–(binds2)–>adapters–(binds2)–>Integrins–(binds2)->ECM*
- Force on epithelium is “transferred” into the matrix itself which has strong matrix protein collagen!
Cadherins are ___ dependent and _____
B: What are the 4 types of Cadherins?
A: Cadherins are Class of Adhesion molecules that are..
1) Ca+ dependent and when Ca+ is high they are able to extend out interact with each other with better structure
2) Homotypic/Homophilic specific Binding= {E-cadherin type will only bind to E-cadherin type}
{V-Cadherin type will only bind to V-cadherin type }
allows for cells to identify each other and hang/connect w/each other!
B: E(Epithelial skin) / N(Neurons,heart,muscle) / P(Placenta,breast,epidem)
VE(vascular endothelium)
Signal-Relaying Junctions/Synapse [2]
- complicated junction where adjacent cells have to be held in close proximity to each other using Cadherin or Ig molecules which mediate stable cell-cell adhesion –>and are anchored themselves by innercell actin
- concentrates multiple receptors/proteins at a synapse held together w/scaffold proteins and Actin anchorage
Selectins
2) example?
- low strength adhesion molecules
- single pass transmembrane molecules that binds to carbs (type of lectin) = heterotypic adhesion! {binds something diff than itself}
- transient adhesion
2) ex. E-Selectin= binds to carb lectins of WBC allowing WBC to slow down and eventually allow integrins to full bind the WBC to damaged tissue
Gap/”communicating” Junctions [3]
- Electrically couples adjacent SIMILAR (heart-heart) cells allowing small ions, sugars and molecules to pass thru (NOTHING larger than 1K dalton)
- important in HEART/LIVEr
-connects using 4 transmembrane Connexin proteins=1 bundle [6 bundles form a functional Connexin channel] Type of Connexin bundle arrangement dictates WHAT passes thru [Gap Connexin channel Junction]
ECM (extracellular matrix)
- made of protein, carb and Fibroblast(secretes collagen), Epethelial cells (secretes matrix proteins/basal lamina connection), osteoblast, etc.
- Bears MOST OF MECHANICAL STRESS
Glycosaminoglycans
Very LONG sugar polymer with uronic acid and sulfated sugar = negative charge that attracts Na+ ions and water
-used to make space-filling bulk inbetween cells
Hyaluronan is a type of ____ and has 4 features to know:
*Specialized type of “tunnel” GlycosaminoGlycan that’s VERRRY LONG but most simplest GAG
- Made from basal side and then secreted into the ECM
- Involved in wound repair and embryogenesis by making cell-free space/lumen tunnel in which cells can migrate and move
*Regulates movement of free floating proteins & growth factors by binding to them and creating lumen tunnel for them to diffuse/move in or around
Proteoglycan [3]
2) example?
3) How are these different than Glycoproteins?
- Core Protein with AT LEAST 1 GAG covalently attached to it (core protein has to have one GAG to be a Proteoglycan)
- HiGH carbs content and is long and unbranched
- Wound repair, migration, chemical signaling between cells
2) [ex. Aggrecan(many GAG attached)]
3)Glycoproteins are short small chains, branched and [[LOW in carbohydrate content]]/HIGH in protein
How does Tau hyperphosphorylation actually cause neurodegenerative tangling?
Tau hyperphosphorylation–>Insolubility&Tau aggregation–>DEC in ability to interact w/microtubules–>Eventually no MCT spacing=tangling
