IIIB CELL ADHESION

what are the two types of adhesion

1. transient adhesion

2. tight adhesion

For the rolling of WBCs and RBBs in the blood vessel, what type of adhesion is exhibited

transient adhesion

in the architecture of tissues, what kind of adhesion is exhibited

tight adhesion

what kind of adhesion is exhibited by epithelial sheet cell

tight adhesion

what kind of adhesion is exhibited by nerve cells in the spinal cord

tight adhesion

what kind of adhesion is exhibited by nerve cells in the liver cells

tight adhesion

what kind of adhesions holds the dividing epithelial cells

1. Basal Lamina

2. Intracellular junctions

migration of cells during vertebrate embryo development

1. Neural crest cells move away from the epithelial neural tube

2. Cells migrate along a specific path

3. Cells aggregate/ assemble with each other or with other cells

4. Cells differentiate into nerve cells and satellite cells which makes up the peripheral ganglia

True or false: CAM helps aggregation and differentiation

True

True or false: There would only be differentiation if there is aggregation

What are the fates of the neural crest cells that migrated and aggregated

1. nerve cells

2. satellite cells

these makes up the peripheral ganglia

How are cells guided to their final destinations

1. chemotaxis

2. pathway guidance

this is the secretion of soluble chemicals that attracts cells

chemotaxis

this is the laying down of adhesive molecules along the right path that guide the cells to their finals destinations

pathway guidance

what are the steps to how the body uses chemotaxis kto respond to an infection

1. Activation and attachement- chemoattractants (cytokines) that get released from the site of injury activates the neutrophils (WBC), showing L-selectins and integrins. The endothelial cells at the same time expresses selectins to bind to neutrophils

   • P-selectins

   • E-selectins

   • this will bind to the carbohydrates on the cell surface

   • P-selectins binds to the microvili of the leuokcyte

2. Rolling - Weak, transient bonds form between selectins on the endothelial cells and L-selectins on neutrophil as it rolls down the blood stream

3. Adhesion - Once rolling slows the neutrophils, stronger adhesion molecules called integrins on the neutrophils bind tightly to ICAMs (Intercellular Adhesion Molecules) on the endothelial cells. This step is essential because without strong adhesion, neutrophils would be washed away by the bloodstream and wouldn’t reach the site of infection

4. Transmigration -neutrophils move toward the site of injury by following the concentration gradient of chemoattractants — this is true chemotaxis.
   
   Neutrophils then begin their job of engulfing and destroying pathogens (like bacteria) and releasing enzymes to break down damaged tissue.

What do you call the process that stabilizes tissue architecture

CELL-TO-CELL RECOGNITION SYSTEM

Explain the CELL-TO-CELL RECOGNITION SYSTEM

the cells of THE SAME DIFFERENTIATED TISSUES preferably adhere to one another, and this interaction stabilizes the tissue architecture

What are the evidences that proved that there is a cell to cell recognition system in tissue architecture

1. Radioactive cell binding assay

2. Fluorescent Labelling Assay

Three mechanisms by which cell-surface molecules can mediate cell-cell adhesion.

1. Homophilic Binding

2. Heterophilic binding

3. Binding with a Linker moelcule

where can CAMs be usually located at

1. plasma membrane

2. Cell Junctions

3. Extracellular domains

4. Cytosolic domains

Homotypic vs Heterotypic Adhesion

homotypic adhesion – between cells of the same type

• heterotypic adhesion – between cells of different

types

why is there a need to have CAMs on the cytosolic side of the plasma membrane

for the recruitment of adapter proteins

What is the purpose of adapter proteins, and why is there a need for it to have CAMs

• it connects to the cytoskeleton

• controls protein activity and gene expression in signaling pathways

What is the role of CAMs in signal pathways

When CAMs bind their external ligands (like another cell or the extracellular matrix), their cytosolic domain undergoes a conformational change.

These then recruits specific adapter proteins that activates enzymes, creating signal cascades

thus trigerring the signal pathway

What are the four major families of CAM and which is the only family that is independent of CA2+

1. cadherins

2. Ig superfamily - independent

3. integrins

4. selectins

True or False: CAMs are mosaics of multiple distinct domains

True

Which families of cams exhibits homophilic interactions and Heterophilic interactions

Homophilic interactions

1. cadherins

2. ig superfamily

heterophilic interactions

1. Integrins

2. Selectins

2 distinct classes of CAM based on Ca2+- dependence and differentiate the two

1. Ca2+- dependent CAM

   • tissue specific interaction

2. Ca2+- independent CAM

   • fine tuning of adhesive interactions during development

A family of CAM that is largely responsible for holding cells together and cell sorting

Cadherins

What are the earliest discovered cadherins

• E- cadherin (epithelial cells)

• N- cadherin (nerve, muscle and lens cells)

• P- cadherin (placental and epidermal cells)

what kind of interaction does cadherins exhibit

homophilic binding

how does cadherins sort itself

1. based on the type of cadherins

2. based on the concentration levels of the same type of cadherins

Describe the structure of cadherins

1. dimers

2. Each cadherin monomer has five extracellular cadherin (EC) repeat domains.

3. Calcium binds between these domains at specific hinge regions. Thus, without calcium, cadherins lose their shape and can’t mediate adhesion properly.

what is the minimum concentration of cadherins for dimerization to occur

x> 0.05 mM Ca2+

Another name of E-cadherins

uvomorulin

This type of cadherin is the best characterized and can usually be located where

E-cadherin, adhesion belts

What does the E-cadherin connect

connects cortical actin cytoskeleton

This is the first cadherin expressed during mammalian development

E-cadherin

This type of cadherin drives compaction” during 8-cell stage in mouse embryo development

E-cadherin

True or false: antibodies against Ecadherinblock blastomere compaction,
why?

True, because E-cadherin drives compaction during 8-cell stage in embryo development

What kind of adapter proteins or intracellular attachment proteins attached the Cadherins to the cytoskeleton (actins )

Catenins

What are the monomers of Immunoglobin Superfamily of proteins

one or more Ig-like domains

what are the two type of Ig superfamily of proteins

-N-CAM (neural cell adhesion molecule)

• homophilic binding

- ICAM (intercellular adhesion molecules)

• heterophilic binding

which type of family and specific cam can be found on endothelial cells that binds to integrins on the blood that forms tight adhesions

ICAM

Describe the structure of Ig superfamily

• made up of one more more ig like domains

• attached to fibronectin type III domains

• anchored to the cytoplasmic membrane

What do you call the protein that inhibits the NCAM from binding, and what is its effect

Acide polysialique (NCAM PSA)

• steric hindrance and electrostatic repulsion prevent NCAM molecules from coming close enough to bind properly.

• Without proper NCAM adhesion, cells clump together in disorganized aggregates because specific cell sorting mechanisms break down.

• Blocks NCAM binding → No cell sorting → Cell aggregation and increased mobility

• In cancer, reduced cell adhesion allows cancer cells to break away from the primary tumor and become invasive, aggresive - the spread of cancer
  

What are the two types of effects of polysia-NCAM and their difference

1. repulsive polysia -NCAM interaction

   • both have polysialique

2. Adhesive polysia-NCAM interaction

   • only has one polysialique that binds to the other cell membrane

This type of family of cam causes fine-tuning of cadherin adhesive interactions during development and regeneration

Immunoglobulin Superfamily of Proteins

What cams are involved in cell aggregation and cell sorting in development

cell aggregation - cadherins

cell sorting - Ig superfamily of proteins

Describe the experiment on the development of rodent pancreas

cadherin mutant - causes no formation of islet ( a tissue ), since cadherin facilitates cell aggregation

N-CAM mutant - disorganized islets, there is still aggregation but no sorting

Describe the experiment on the neural development on mice

mutant N-cadherin → die early in devt (embryo doesnt get developed)

• mutant N-CAM → normal but with neural defects

What family does selectins belong to

Lectin family

This family is described to have its cell surface CHO-binding proteins

Selectins

what does selectins usually bind to and what kind of binding does these faciliate

bind to specific oligosaccharides (in glycoproteins and glycolipids) in another cell

heterophilic binding

type of cam that mediate transient cell-cell adhesion in the bloodstream during inflammation responses

Selectins

On what cells can you find L-SELECTIN

WBC

On what cells can you find P-SELECTIN

blood platelets and endothelial cells (activated during inflammatory response only )

On what calls can you find E-SELECTIN

Activated endothelial cells

Describe the structure of Selectins

1. bounded to endothelium leukocytes

2. has short consensus repeats ( varies per type, shortest being L,E,P)

3. different type of domains

• EGF domains - P

• C TYPE Lectin domain - E

difference of adhesion types between selectin dependent and integrin dependent binding when it comes to inflamatory response

1. Selectin Dependent - weak adhesion/ Transient adhesion and rolling

2. Integrin Adhesion - tight adhesion/ strong adhesion and emigration

these CAMS are what you calls the “integrators” or linker proteins

integrins

two types of ingegrins

cell to matrix → ties the matrix to the cell’s cytoskeleton

• cell to cell → may also activate intracellular signaling

pathways

describe the structure of your integrins

1. 2 non-covalently-associated transmembrane glycoproteins α and β, thus a heterodimer

2. has two domains, the exxtracellular matric for LIGAND BINDING SITE and the cytosolic domain for CYTOSKELETON BINDING SITES

how many integrin heterodimers are present that causes different combinations of B and a chains

20

what are the possible reasons for the great diversity of integrins

1. 20 integrin heterodimers and its different combinations

2. alternative splicing of integrin RNA

What are the different types of integrins

• β1 integrins – ubiquitous, muscle

• β2 integrins – WBC

• β3 integrins – platelets

What genetic disease gets induced when there is deficient B2 integrins

Leucocyte adhesion deficiency (repeated bacterial infection as this affects the WBC)

What genetic disease gets induced when there is deficient B3 integrins

Glazmann’s diesease (excessive bleeding )