9-9 Cell Junctions, Adhesion & Matrix

Question 0

Cell-Cell Anchoring Junction [2]

Answer 0

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

Question 1

Briefly describe the 2 BIG types of Tissue environments

Answer 1

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

Question 2

Occluding/TIGHT Junction

AKA ____ _____

Answer 2

cell TIGHT junction that seals gap between epithelial cells using “Fence” and sealing techniques

AKA (Zonula Occuldens)

Question 3

Channel-Forming JUnctions

Answer 3

GAP junction that allows passage of small water-soluble molecules from cell to cell

Question 4

1) What are the 2 different ways a cell may be anchored to the Basal membrane?
2) These both are WHAT TYPE OF JUNCTIONS?

Answer 4

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

Question 5

What are the 4 functional classes of Cell Junctions?

Answer 5

1. Anchoring Junctions=cell-to-matrix adhesion and cell-to-cell adhesion
2. 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)
3. Channel-Forming junctions= “GAP” Junctions tht allow small ions and sugars to get inbetween cells
4. Signal-Relaying Junctions = complex junctions that uses combination of other junctions

Question 6

A. What is Paracellular Transport

B. What about “Fence” function

Answer 6

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

Question 7

What is the Tight/Occluding Junction actually made of? [2]

Answer 7

Claudins MAJOR proteins that form Zip-locks on apical aspect of lateral membrane surface of sealed cell
**Occludins help to but are minor

Question 8

Transcellular Transport

Answer 8

Transporter proteins on diff. sides of the cell utilizing “fence” function to transport/regulate molecules moving thru/across the cell

Question 9

Explain the types of Anchoring Junctions

Answer 9

Transmit stress from 1 cell to the next cell

1. Cell-Cell (Adherens vs. Desmosome)
2. Cell-Matrix (Focal adhesion vs. Hemidesmosome)

Question 10

Describe the Adherens Junction specifically [4]

Answer 10

• 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

Question 11

Desmosomes

2) What are Plaques?
3) What are “Rivets” ?

Answer 11

• 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”

Question 12

How is Auto-immune dz linked to Desmosomes?

Answer 12

Pt body developes antibodies against desmosomal cadherins leading to blistering and fragile fragile skin and esphogeal problems !

Question 13

Describe Focal Contacts (AKA Focal Adhesions) [3]

2)What are these important for?

Answer 13

• 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]

Question 14

HEMIdesmososme “Half-Desmosome” [2]

Answer 14

• 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!

Question 15

Cadherins are ___ dependent and _____

B: What are the 4 types of Cadherins?

Answer 15

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)

Question 16

Signal-Relaying Junctions/Synapse [2]

Answer 16

• 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

Question 17

Selectins

2) example?

Answer 17

• 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

Question 18

Gap/”communicating” Junctions [3]

Answer 18

• 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]

Question 19

ECM (extracellular matrix)

Answer 19

• made of protein, carb and Fibroblast(secretes collagen), Epethelial cells (secretes matrix proteins/basal lamina connection), osteoblast, etc.
• Bears MOST OF MECHANICAL STRESS

Question 20

Glycosaminoglycans

Answer 20

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

Question 21

Hyaluronan is a type of ____ and has 4 features to know:

Answer 21

*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

Question 22

Proteoglycan [3]

2) example?
3) How are these different than Glycoproteins?

Answer 22

• 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

Question 23

How does Tau hyperphosphorylation actually cause neurodegenerative tangling?

Answer 23

Tau hyperphosphorylation–>Insolubility&Tau aggregation–>DEC in ability to interact w/microtubules–>Eventually no MCT spacing=tangling

Question 24

Collagen [5]

2) What is Scurvy?

Answer 24

Collagen is most common structural protein
ºTriple-stranded polyproline[proline or hydroxyproline] alpha helical chains

ºResponsible for strength of ECM
ºLong stiff rod sturcutre w/Hydrogen bonding between [OH] of diff alpha chains = stability

ºalso forms Lysine intra-molecule cross-linking
—(forms)——>Cables

2) Scurvy= Vitamin C is a cofactor for creating Hydroxyproline and loss of [OH] from Hydroxyproline in collagen –> leads to loss of H-bonding and breakdown of collagen

Question 25

Describe Collagen Synthesis and composition [3]

Answer 25

• Highly ordered collagen is Made in the ER and becomes modified-glycosylated in Golgi.
• Contains Carboxy-Amino term peptides that keep molecule soluble but are cleaved off after secretion–>mature collage molecule—>a bunch of these make COLLagen FIBrils (found in tendons, etc. )

*has covalent and non-covalent lateral striated interactions

Question 26

Type 9 Collagen

Answer 26

Associated w/cartilage and laterally associates with Type II fibrils. Defect can lead to osteoarthritis

Question 27

Type I Collagen

2) What’s the catch w/Collagen composition?
3) Ehlers-Danlos Syndrome?

Answer 27

• *90% of collagen in body is Type I –>& used to make long fibrils. Also are analogous to strong intermediate filaments.
• prominent in bone, skin, tendons and ligaments

2) Each collagen is made of multiple varied subunits to give different types of collage fibrils
3) comes from mutations in collagen maturation/secretion Types I,III or V–>hyperelastic skin

Question 28

1) Type 4 Collagen

2) Type 7 Collagen?

Answer 28

1) sheetlike network that makes up the basal lamina on which Epethelial cells sit on
2) = makes up anchor fibrils tht links basal lamina to the matrix beneath it

Question 29

Elastin [4]

Answer 29

Gives tissue elasticity (Like blood artery vessels)

• Highly cross-linked and is the MAJOR ECM of arteries
• Super Rubber band that can stretch out
• Has Fibrillin that covers elastin fibers and is essential for giving elasticity to elastin

Question 30

Marfan’s Syndrome

Answer 30

Fibrillin mutation which DEC elasticity in big artieries–>aortic ruptures and skeletal abnormalities

Question 31

Basal Lamina [3]

4) How is it related to Cancer?
5) Explain why BL is important in Positional Regeneration of neuromuscular junctions?

Answer 31

1) specialized ECM protein that allows and is secreted by cells who sit on it–> surrounds fat, muscle, Schwann cells , etc.
2) Has adhesive glycoproteins in it and In the Kidney functions as molecular filter (selective as to what it allows to get thru)

3) Important for cell survival via signals (Sends positive and proliferation signals for cell survival) = Anchorage dependence!
4) Polarizes and orients the cell(Fibronectin fibrils & cytoskeleton) while BLOCKing cell migration as a glued barrier. (Cancer cells obtain ability to degrade basal lamina and move about :-()
5) Keeps connective separate from epithelial tissue and provides info to cells of where to go and where they are [neurons and muscular receptors regenerate in the SAME SPOT every single time due to info sent out from the BL]

Question 32

Fibronectin [4]

Answer 32

ºAdhesive ECM Glycoprotein that binds well to collagen, other fibronectin, matrix {heparin}

ºhas RGD (Arg-Gly-Asp) binding motif that binds to integrins

ºDirects cell migration during development
º 2 Large subunits connected by disulfide bond = Dimer

Question 33

What proteins can be found in the Basal Lamina [6]

Answer 33

Basal Laminas forms a sheet and allows A LOT of matrix proteins to stick together: These proteins are found in BL»

• Laminin(binds cells, collagen, GAG, PG)
• Fibronectin
• Type 4 Collagen [network forming collagen]
• Perlecan proteoglycans
• Nigoden glycoprotein
• Heparin Sulfate [glycosaminoglycan]

Question 34

1) WHat are Integrins
2) Explain the Beta chain linkage in Integrins?
3) What type of Specificity do Integrins have to their ligands?

4)What does a5B1 Integrin mean?

Answer 34

-ECM dimer protein (alpha and beta chain) that binds to mostly [RGD] sequences on 1 side and then Basal Lamina membrane of outer cell on other side

2) Beta chain is usually linked to actin cytoskeleton element BUT in Hemidesmosomes-> Integrins are linked to Intermediate Filaments instead
3) Overlapping specificity (Ligand it binds depends on which alpha and beta subunit comes together)!

4)a5B1= 5 alpha subunits in a chain and 1 Beta subunit in a separate chain all found in 1 Integrin dimer

Question 35

How do Integrins actually relay signals? [2]

2. What are examples of these 2?

Answer 35

2 types:
1: “inside–> out”= inactive integrin on cell surface is activated by INNER cell event which makes it bind to outside ECM protein
(ex. Platelets activate B3 to bind fibrinogen–>aggregation and clot OR T-lymphocytes and B2 integrins)
_————————————————————————–

2. “OUTSIDE–>IN”= eager Integrin on outside cell surface binds to outside ligand ECM protein –>integrins start to cluster at that area and eventually sends signal INSIDE CELL “activation” !
   (ex. outside ECM ligand binding occurs–>Focal Adhesion Kinase is recruited& clusters up–> activates inner cell to proliferate, survive or migrate)
   * SIMILAR TO GROWTH FACTOR RECEPTORS

Question 36

Which integrin subunit is the most “promiscuous” and what does that even mean?

Answer 36

B1 Integrin subunits are MOST promiscuous because they can partner up with at least 12 different alpha subunits to make an Integrin

Question 38

What are 2 examples of inside–>out Integrin signaling?

Answer 38

1) Platelets inside cell activate inactive B3 integrin [on cell surface] to bind to ECM fibrinogen and aggregate/clot!
2) inner T-lymphocytes factors activate cell surface B2 integrin to bind to antigen presenting cells in the matrix

Question 39

Pemphigus

Answer 39

Autoimmune Dz where body creates Antibodies tht destroy Desmosomal Cadherins/Desmogleins = blistering

Question 40

Integrins are ____ OR ____ DEPENDENT in order to bind cytoskeleton filaments and ECM stuff

2) What others are deponent on these molecules?

Answer 40

Integrins are BOTH Ca+ OR Mg+ DEPENDENT–>needed to bind cytoskeleton filaments and ECM stuff

2) SELECTINS AND CADHERINS are Ca+ dependent!