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67 terms

Histology-Cell Adhesion Molecules

Histology-Block I
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What is a cell adhesion molecules?
Cell adhesion molecules are groups of transmembrane proteins that mediate cell-cell and cell-extracellular matrix interactions.
What are the four examples of cell adhesion molecules given in the lecture?
1. integrins
2. cadherins
3. Immunoglobulin superfamily
4. selectins
What is the function of integrins?
They have a dual function: they bind to the extracellular matrix and the internal cytoskeleton. Interaction of cells with ECM is key to tissue integrity and organization.
Describe the alpha subunit of the integrin.
The alpha subunit of an integrin has two chains linked by a disulfide linkage and a globular head with binding sites for divalent cations.
Describe the beta subunit of integrins.
The beta subunit has two significant characteristics: (1) The extracellular chain contains repeating cysteine-rich regions (2) The intracellular portion interacts with actin filaments through 3 connecting proteins: talin, vinculin, and alpha-actin.
What RGD sequence do integrins bind to ECM proteins?
RGD sequence Arg-Gly-Asp
Cadherin: The four domains in the extracellular portion of cadherin bind to _____.
Calcium
What is the function of cadherins?
Cadherins are the main adhesion proteins holding epithelial cells together in a sheet arrangement.
Cadherins: The cytoplasmic tail interacts with _____ filaments through numerous intracellular attachment proteins, including three catenin proteins.
actin
Cadherins have been found in a variety of tissues and are located at ______.
Zonula adherens= belt desmosomes in intestinal epithelial cells.
Ar zonula adherens, belt desmosomes, cadherins interact with?
spectrin-like and ankyrin-like proteins (the catenins) associated with actin filaments at adherent junctions (belt desmosomes)
Members of the immunoglobulin superfamily include?
1. T-cell receptors
2. Immunoglobulins (Ig)
3. CD4 and CD8 glycoproteins
4. Class I and Class II glycoproteins from Major Histocompatibility Gene Complex
5. Neural cell adhesion molecules-function to attach neurons to glial cells or neurons to ECM
Can the Immunoglobulin superfamily antigens contribute to homotypic cell-cell adhesion (two phenotypically similar cells) and heterotypic cell-cell adhesions (two phenotypically dissimilar cells)?
Yes
What two molecules play an important role in T cell interactions and binding of leukocytes to activated or resting endothelial cells?
ICAMS and VCAMS
What characteristic makes CAMs belong to the immunoglobulin (Ig) superfamily of proteins?
The extracellular segment of a cell adhesion molecule or CAM is folded into 2-6 immunoglobulin-like domains.
Where are selectins located in the body?
Selectins are located at the surface of blood cells, platelets, and endothelial cells.
An absence of E-selectin results in a disease called?
Leukocyte adhesion deficiency Type 2.
E-selectin recognizes a specific oligosaccharide on the glycolipids and glycoproteins of neutrophils allowing these cells to attach to endothelial cells at the inflammation site.
What are the 3 major types of selectins?
1. L-selectin: carried by lymphocytes and with binding affinity to sulfated carbohydrates.
2. E-selectins: expressed by activated endothelial cells
3. P-selectin: expressed by platelets and activated endothelial cells
The lymphocyte-endothelial cell interaction requires two types of cell adhesion proteins:?
1. Selectins
2. Integrins
High Endothelial Venules (HEVS) are found where in the body?
In humans, HEVs are found in all secondary lymphoid organs (with the exception of spleen, where blood exits through open arterioles and enter the red pulp),
What is the function of HEVs?
HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system. HEV cells express addressins, which are specific adhesion molecules that attach to the L- selectins on lymphocytes and anchor them to the HEV wall in preparation for crossing the endothelium.
What types of junctions can be found in epithelial cells?
Occluding junctions
What is usually found below occluding or tight junctions?
Zona adherens
What proteins contribute to the tight/occluding junctions?
Occludin, claudin and associated proteins.
Where are tight junctions found?
They are only found in epithelial cells. They are found in capillaries of the brain and form the blood brain barrier. They are located between hepatocytes to seal the bile canaliculi to prevent the leakage of bile.
What proteins are found in tight junctions?
The protein of the occludin family
What is an exception to tight junctions?
Bile canaliculi, cell membranes of hepatocytes form these structures.
Zona occludins aka?
Tight Junctions
What is the function of zona adherens?
Cell-cell attachment sites.
What is the protein involved in zona adherens/belt desomosomes?
Cell adhesion molecule is cadherin
Zona adherins is found below what junction?
Found just basal to the zonula occludens of intestinal epithelial cells.
What 4 junctional complexes are arranged along the lateral surfaces of columnar epithelial cells from apical end to basal lateral end?
1. Occluding junctions or zona occludens-selective permeability barrier
2. Zona adherens or belt desmosome- cell to cell attachments
3. Macula adherens or spot desmosome
4. Gap junction- communicating junction
The zonula adherens is associated with ____microfilaments
actin
This association in, zonula adherens, is mediated by the interaction of ____ with _____.
a. cadherins
b. catenins (α, β, and γ).
Desmosomes aka?
Macula adherens
The macula adherens is a spotlike junction associated with _____ intermediate filaments.
keratin
Macula adherens can be found where on the cell?
Lateral and basal cell surfaces.
Are also present in the intercalated disks linking adjacent cardiocytes in the heart and in the meninges lining the outer surfaces of the brain and spinal cord.
What is the functon macula adherens?
Provide strength and rigidity to an epithelial cell layer.
The macula adherens is found right below what junction?
The zonula adherens
Macula adherens have ____ serving at the attachment sites for intermediate filaments.
Desmoplakins.
At the cytoplasmic surface of the macula adherins, the plasma membrane is thickened by the presence of ____.
Desmoplakins
What is a cell adhesion molecule is involved in the macula adherens?
Desmogleins
What makes the zonula adherens and the macula adherens different from the occluding junctions?
Adjacent cell membranes are separated by a relatively wide intercellular space.
The wide intercellular space in the zonula adherins and macula adherens is made up by what two cadherin proteins?
Desmogleins and desmocollins
What is the cytoplasmic plaque in the macula adherens made up of?
Cytoplasmic plaques containing desmoplakin and plakoglobulin proteins
Hemidesmosomes are ___-___ attachments involving intermediate filaments.
cell to matrix attachments
In hemidesmosomes, at the sites of attachment the cell membrane is thickened into plaques into which insert _____.
Intermediate filaments
How are hemidesmosomes biochemically dissimilar to desmosomes?
None of the adhering proteins of desmosomes are found in hemidesomosomes. The cytoplasmic surface serves as attachment sites for intermediate filaments.
Where are hemidesmosomes found?
They are found at the base of epithelial cells, firmly anchor cells to the underlying basement membrane.
Some of the proteins in hemidesmosomes that anchor cells to the ECM are ______ and ______.
a. alpha6 beta 4 integrins
b. bullous pemphigoid antigens (collagen XVII)
Why are the proteins in hemidesmosomes clinically important?
These proteins are important in understanding painful blistering diseases, autoimmune diseases which result in the separation of epithelial cells from the basement membrane and the filling of the open space with fluid.
What enzymes does a neutrophil release and what action can it have on the hemidesmosomes?
Eosinophils release proteases causing the breakdown of anchoring filaments linking the attachment plaque of the hemidesmosome to the basal lamina. A blister develops.
What is the antigen involved in the autoimmune acantholytic blistering disease, pemphigus foliaceus?
Desmoglein 1
Desmoglein 1 is associated with what junctional complex?
Macule adherens
_____ allow the passage of small signaling molecules between adjacent cells to coordinate responses.
Gap junctions
What is the major protein in a gap junction?
Connexin, a major protein component, forms hexamers or connexons in the shape of cylinders.
What junction defines the cell polarity and allows the passage of substances between adjacent cells?
Tight junctions
Zonula aderens is associated with _____ filaments.
Actin
Which junction has a belt like distribution?
Zonula adheren
Which junction is associated with intermediate filaments?
Macula adherens or spot desmosomes and hemidesmosomes
Which junction links the basal domain of an epithelial cell to the basal lamina?
Hemidesmosomes
Which junction is formed by connexons, a channel-like structure that enables the passage of small molecules between cells?
Gap junction
____, _____, and _____ junctions can all have signaling functions in addition to their structural roles.
Anchoring, occluding, and channel-forming junctions
Are gap junctions associated with cytoskeletal components?
No, they are not.
For Zonula adherens junction:
What is the extracellular ligand, the intracellular cytoskeletal attachment and the intracellular anchor proteins?
Extracellular ligand= Cadherin in neighboring cell
Intracellular cytoskeletal attachment= Actin filaments.
Intracellular anchor protein= catenin
For Macula adherens:
What is the extracellular ligand, the intracellular cytoskeletal attachment and the intracellular anchor proteins?
Extracellular Ligand: Cadherin (desmoglein and desmocollin)
Intracellular cytoskeletal attachment: Keratin Intermediate filaments
Intracellular anchor proteins: Plakoglobin, plakophilin, desmoplakin
Integrins are associated with what intracellular cytoskeletal attachment?
actin filaments