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M1-C2-L19 --> Cell to Cell Communication

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What are the three type of junctions found in cells?
1. Occluding junction
2. Anchoroing junctions
3. Communicating junctions
What are occluding junctions seen in vertebrates only?
Tight junctions (Zonula Occludens)
Another name for tight junctions is?
Zonula occludens
What are the two general function of zonula occludens?
1. To provide a barrier role in most epithelia.

2. To seal epithelial cells together.
Permeability of epithelial lining decreases with an increase in what?
Number of sealing strands
Give three examples of transmembrane tight junction proteins.
1. Occludin
2. Claudin
3. JAM (Junctional Adhesion Molecule)
What is unique about JAM as opposed to Occludin or Claudin?

JAM is a single pass transmembrane protein
Which part of the transmembrane tight junction protein is there an effector bind to molecules such as ZO-1?
On the cytoplasmic tail end
ZO proteins bind to what type of transmembrane proteins?

Occludins and/or Claudins and/or JAM
ZO's are almost always associated with what type of filaments?

Actin filaments
ZO's belong to what type of family?

MAGUK (Membrane Associated Guanine Kinase) family
Loss of ZO's will lead to increase in what?
Permeability
What is the purpose of anchoring junctions?
Provide mechanical strength against mechanical stress
What to anchoring junctions connect? X 2
1. Cytoskeleton to neighboring cells.
2. Cytoskeleton to matrix
What are the types of anchoring junctions and give their connections? X 4
1. Focal Adhesions (cell-ECM)
2. Adherens junctions (cell-cell)
3. Desmosomes (cell-cell)
4. Hemidesmosomes (cell-ECM)
What are the two main classes of proteins in anchoring junctions?

1. Intracellular anchor proteins
2. Transmembrane adhesion proteins

What is 1 and 2?

1. Intracellular anchor proteins
2. Transmembrane adhesion proteins
Adheren junctions connect what between cells?
Bundles of actin filaments.
Where do you expect to find anchoring junctions?
Muscle, skin, heart
What are Zonula Adherens?

Adhesion belts of adheren junctions
Catenin is an example of what?
Intracellular anchoring protein
Transmembrane adhesion proteins of anchoring junctions belong to what type of family?
Cadherin family
In order for tight junctions to form, cells must be attached by what?
adheren junctions
What is the character of the Cadherin family?
Calcium dependent cell-cell adhesion.
Where are two places where cadherins can be found?
Adherens junctions and desmosomes.
Under what condition do cadherin junctions occur?
Calcium levels must be greater than 1 mM.
Types of classical cadherins and where they are found X 4.
1. P-cadherins (placenta, epidermis, breast epithelium)

2. E-cadherins (epithelium)

3. N-cadherins (neurons, heart, skeletal muscle, lens, and fibroblasts)

4. VE-cadherins (endothelial)
The cytoplasmic tail of classical cadherins are linked to actin cytoskeleton by what?

Catenins (alpha and beta) and p120 protein
What is the purpose of p120?

To regulate cadherin function
What is the purpose of catenin beta?

Functions in intracellular signaling.

How does adherens junctions involved in development?

Tightening along selective adhesion belts will invaginate regions of cell sheet to produce epithelial tube.
What is the purpose of catenin alpha?

To associate with actin filaments
What is the purpose of focal adhesions?

To connect actin filaments to the basal lamina.
Transmembrane proteins of the focal adhesion junctions belong to what family?
Integrin family
Integrins can trigger what?
Focal Adhesion Kinase (FAK)
What is the function of focal adhesion junction assembly and activation?
Assembly and activation serve as signaling events in modulating ENDOTHELIAL PERMEABILITY.
What do desmosomes connect?
Connects intermediate filaments (IF) between cells.
What type of IF does desmosomes attach?
Cell specific, but it is keratin in most epithelial cells.
Transmembrane adhesion proteins of desmosomes belong to what family?
Cadherin family
Examples of transmembrane adhesion proteins of desmosomes. X 2
1. Desmoglein
2. Desmocollin
Examples of Intracellular anchoring proteins of desmosomes.
1. Plakoglobin (gamma catenin)
2. Desmoplakin
What does hemidesmosomes connect?
Intermediate filaments to the basal lamina.
Transmembrane proteins of hemidesmosomes belong to what family?
Integrin
Intracellular anchor protein of hemidesmosomes.
Plectin
Desmosomes and hemidesmosomes play an integral role in resisting mechanical stress (thus anchoring junctins), but due to their sensitivity to environment cues, they also play what other vital role? X 5.
1. Tissue remodeling
2. Differentiation
3. Wound healing
4. Invasion
5. Signal Cascades
Gap junction is what type of major junction?
Communicating junction
What are connexins?
Membrane-spanning, channel-forming proteins of gap junctions (will assemble to become connexOn)
What is the maximal pore size of connexons?
1.5 nm
What do connexins allow for passing and what does it not allow?
Allows small molecules, but NOT proteins.
A connexon is made up of how many monomers?
Six monomers
Each connexin monomer is made up of how many membrane-spanning segments?
Four membrane-spanning segments.
What are the functions of gap junctions? X 3
1. Electrical synapse
2. Sharing of metabolites
3. Communication during development
Describe the benefits of electrical synapse function for gap junctions.
Direct coupling allows propagation of an action potential from one cell to another without the need for a chemical intermidiate (much faster)
Give an example of metabolite sharing seen in gap junctions.
Hepatocytes not stimulated by a hormone, b/c many layers away from capillary/source of hormone, will detect signal by sharing a secondary messenger via gap junctions.
Where do you see gap junctions during development?
Between granulosa cells AND oocyte
Mutation in connexin leads to what?
Infertility and disruption in the development of both oocyte and granulosa cells.
What regulates gap junction permeability?
1. pH
2. Cytosolic calcium
3. Extracellular signals (neurotransmitters)
Give an example of an extracellular signal that affects permeability of gap junctions.
Dopamine
Why regulate permeability?
Cells need a way to close down connections to prevent widespread damage when one participant is damaged.
Non-junctional cell-cell adhesion involves what families?
1. Immunoglobulin superfamily
2. Cadherin
3. Selectin
4. Integrin
Describe the three types of cell-cell adhesion mechanisms
1. Homophilic binding
2. Heterophilic binding
3. Binding through an extracellular linker molecule.
Why cell-cell adhesion?
Before cells can form junctions, they need to adhere or stick ot each other.
What generalized molecule is responsible for cell adhesion?
Cell Adhesion Molecule (CAM)
Cadherins mediate cell-cell adhesion by what mechanism?

Homophilic mechanism
Selectins mediate what and where?
Mediates cell-cell adhesion in bloodstream.
Selectins are found on what part of the cell?
Cell surface
Selectins bind what?
Carbohydrates
Selectins are dependent on what?
Calcium
What are the subtypes of selectin?
L-selectin
P-selectin
E-selectin
What type of cells are associated with L-selectin?
White blood cells (Leukocytes)
What type of cells are associated with P-selectin?
Platelets and endothelial cells.
What type of cells are associated with E-selectin?
Activated Endothelial cells
What type of WBC character is seen when on top of endothelial sheet with selectin dependent movement?
Weak adhesion and ROLLING
Give two examples of Calcium independent adhesion.
1. Neural Cell Adhesion Molecules (N-CAMs)
2. Intercellular Cell Adhesion Molecules (I-CAM)
N-CAMs belong to what family?
Immunoglobulin superfamily
Impaired desmosome functions can induce what disorders?
Severe skin disorders
Mutations in the genes of the desmosomal plaque proteins plakoglobin and desmoplakin have been linked to what disease?
Cardiomyopathy

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