Cell Adhesin
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CELL BIOLOGY
LESSON 19: CELL ADHESION MOLECULES Learning Objectives
Local chemical mediators at the site of inflammation signal the endothelial cells to express P-selectin.
In this lecture, you will learn •
Discussion on cell adhesion molecules
•
Their role in maintaining in integrity of cell attachments
The molecules which help in cell to cell binding are called cell adhesion molecules A. Calcium Dependent Adhesion Molecules (Cadherins)
There are over a dozen different types of these molecules. Almost all vertebrate cells express one or more cadherins. Extracellular domains are seen. They contain calcium binding sites. They bind in a homophilic pattern, i.e. one cadherin binds to another in the extracellular space. Thes molecules connects cells together at specialized junctions. They may mediate interactions between the cells’ actin cytoskeletons. The amino acid sequence His-Ala-Val may be involved in the actual “homophilic” binding. Intracellular domain binds to specific proteins in the cytoskeletal system. Table 3-1 Well known types of Calcium dependent adhesion molecules
E-Cadherin; P-Cadherin Desmosomal Cadherin
What tissues?
epithelial cells epidermis and placenta N-Cadherin nerve, muscle, lens cells
Structure: Intracellular binding proteins adhesion catenins, belts alpha actinin desmosomes desmoplakins I, II; Plakoglobin adhesion catenins, belts alpha actinin, vinculin
Cytoplasmic filaments
Binding is relatively weak and the cells roll along the endothelial cell until they bind more tightly by their integrins (see below). Integrin binding is tighter and stimulates the cell to crawl out of the blood vessel Integrins are also transmembrane binding glycoproteins that usually bind cells to matrix. However, they also may bind cells to cells. Binding is calcium dependent. Binding is from an integrin to a specific ligand on the target cell. Binding may involve actin filaments, but is not associated with a cell junction. Integrins contain an alpha and a beta subunit: Most cell to cell interactions involve integrins with an alpha and a beta-2 subunit example. Integrins on white blood cells allow tighter binding to endothelial cells before they migrate out of the blood stream to tissue. LFA-1 (white blood cells); Mac-1 (macrophages) Humans with a genetic disease called “leucocyte adhesion deficiency” are unable to synthesize the Beta-2 subunit. Thus, the white blood cells lack the entire family of beta-2 receptors needed to bind to endothelial cells. They suffer repeated bacterial infections. D. Non-Calcium Dependent Cell to Cell binding
actin keratin; desmin actin
B. Cell to Cell Surface Carbohydrate Binding Proteins (Selectins)
They are transient transmembrane binding proteins (lectins In the presence of Calcium, they bind to specific oligosaccharides on another cell They help in Heterophilic” cell adhesion (binding protein binds to another type of site on a cell Example P-Selectins allow the initial binding of white blood cells to endothelial cells
70
Thus, they are bound at this inflammatory site by the endothelial cells.
C. Cell to Cell binding through Special Integrins
They contain about 100 amino acid residues.
Type of Cadherin
Nearby neutrophils express the oligosaccaride on both the glycolipids and glycoproteins in their membrane. Thus, they are bound at this inflammatory site by the endothelial cells
They belong to the immunoglobulin (Ig) superfamily; NCAM’s, ICAMs and L1 are examples. They are single pass, transmembrane proteins which may bind to the cytoskeletal system inside the cells. Outside the cell, the binding may be homophilic (to each other) or heterophilic (to another molecule Cells may have N-CAMs and Cadherins, but the N-CAM binding is not as strong as the cadherin binding. Examples N-CAM (neural cell adhesion molecule) is actually expressed by a variety of cell types., including nerve cells; binds by homophilic interactions ICAM (intercellular adhesion molecules) may be expressed on activated endothelial cells. Theseare the target ligand for the integrins expressed by white blood cells (heterophilic binding L1 is a neural cell to cell adhesion molecule important in developing nerve processes E. Cell to Matrix Binding: Integrins
Cells can be influenced heavily by the environment (matrix proteins) because of the presence of transmembrane glycoproteins called Integrins
© Copy Right: Rai University
2.102
CELL BIOLOGY
Extracellular matrix receptors that have selective affinity for certain matrix proteins. Bind with relatively low affinity (Ka= 106-109 liters/mole): this provides a “velcro effect” that allows cells to explore their environment Binding is calcium and magnesium dependent. Extracellular site is with a ligand in the matrix. Intracellular site may be with proteins associated with the actin cytoskeleton (talin and alpha actinin); some integrins bind to intermediate filaments, however. Integrins have an alpha and a beta subunit (heterodimer). Subunits can be diverse (different types) by alternative splicing Specificity of binding depends on the combination of alpha and beta subunits For example Cells with alpha-6, beta-4 integrins have hemidesmosomes. Bind matrix proteins in the basal lamina (like laminins) and intermediate filaments, like keratins, in the cytoplasm White blood cells have alpha1 and beta 2 integrins that bind to endothelial cells. Macrophages have alpham and beta 2 integrins that also bind to endothelial cells. Platelets have beta 3 subunit in their integrins that allows them to bind fibrinogen during blood clotting. Humans with Glanzmann’s disease are genetically deficient in beta 3 containing integrins. These patients bleed excessively Cells with alpha 5 and beta 1 integrins bind fibronectin in the extracellular matrix.
Notes
2.102
© Copy Right: Rai University
71
LESSON 19: CELL ADHESION MOLECULES Learning Objectives
Local chemical mediators at the site of inflammation signal the endothelial cells to express P-selectin.
In this lecture, you will learn •
Discussion on cell adhesion molecules
•
Their role in maintaining in integrity of cell attachments
The molecules which help in cell to cell binding are called cell adhesion molecules A. Calcium Dependent Adhesion Molecules (Cadherins)
There are over a dozen different types of these molecules. Almost all vertebrate cells express one or more cadherins. Extracellular domains are seen. They contain calcium binding sites. They bind in a homophilic pattern, i.e. one cadherin binds to another in the extracellular space. Thes molecules connects cells together at specialized junctions. They may mediate interactions between the cells’ actin cytoskeletons. The amino acid sequence His-Ala-Val may be involved in the actual “homophilic” binding. Intracellular domain binds to specific proteins in the cytoskeletal system. Table 3-1 Well known types of Calcium dependent adhesion molecules
E-Cadherin; P-Cadherin Desmosomal Cadherin
What tissues?
epithelial cells epidermis and placenta N-Cadherin nerve, muscle, lens cells
Structure: Intracellular binding proteins adhesion catenins, belts alpha actinin desmosomes desmoplakins I, II; Plakoglobin adhesion catenins, belts alpha actinin, vinculin
Cytoplasmic filaments
Binding is relatively weak and the cells roll along the endothelial cell until they bind more tightly by their integrins (see below). Integrin binding is tighter and stimulates the cell to crawl out of the blood vessel Integrins are also transmembrane binding glycoproteins that usually bind cells to matrix. However, they also may bind cells to cells. Binding is calcium dependent. Binding is from an integrin to a specific ligand on the target cell. Binding may involve actin filaments, but is not associated with a cell junction. Integrins contain an alpha and a beta subunit: Most cell to cell interactions involve integrins with an alpha and a beta-2 subunit example. Integrins on white blood cells allow tighter binding to endothelial cells before they migrate out of the blood stream to tissue. LFA-1 (white blood cells); Mac-1 (macrophages) Humans with a genetic disease called “leucocyte adhesion deficiency” are unable to synthesize the Beta-2 subunit. Thus, the white blood cells lack the entire family of beta-2 receptors needed to bind to endothelial cells. They suffer repeated bacterial infections. D. Non-Calcium Dependent Cell to Cell binding
actin keratin; desmin actin
B. Cell to Cell Surface Carbohydrate Binding Proteins (Selectins)
They are transient transmembrane binding proteins (lectins In the presence of Calcium, they bind to specific oligosaccharides on another cell They help in Heterophilic” cell adhesion (binding protein binds to another type of site on a cell Example P-Selectins allow the initial binding of white blood cells to endothelial cells
70
Thus, they are bound at this inflammatory site by the endothelial cells.
C. Cell to Cell binding through Special Integrins
They contain about 100 amino acid residues.
Type of Cadherin
Nearby neutrophils express the oligosaccaride on both the glycolipids and glycoproteins in their membrane. Thus, they are bound at this inflammatory site by the endothelial cells
They belong to the immunoglobulin (Ig) superfamily; NCAM’s, ICAMs and L1 are examples. They are single pass, transmembrane proteins which may bind to the cytoskeletal system inside the cells. Outside the cell, the binding may be homophilic (to each other) or heterophilic (to another molecule Cells may have N-CAMs and Cadherins, but the N-CAM binding is not as strong as the cadherin binding. Examples N-CAM (neural cell adhesion molecule) is actually expressed by a variety of cell types., including nerve cells; binds by homophilic interactions ICAM (intercellular adhesion molecules) may be expressed on activated endothelial cells. Theseare the target ligand for the integrins expressed by white blood cells (heterophilic binding L1 is a neural cell to cell adhesion molecule important in developing nerve processes E. Cell to Matrix Binding: Integrins
Cells can be influenced heavily by the environment (matrix proteins) because of the presence of transmembrane glycoproteins called Integrins
© Copy Right: Rai University
2.102
CELL BIOLOGY
Extracellular matrix receptors that have selective affinity for certain matrix proteins. Bind with relatively low affinity (Ka= 106-109 liters/mole): this provides a “velcro effect” that allows cells to explore their environment Binding is calcium and magnesium dependent. Extracellular site is with a ligand in the matrix. Intracellular site may be with proteins associated with the actin cytoskeleton (talin and alpha actinin); some integrins bind to intermediate filaments, however. Integrins have an alpha and a beta subunit (heterodimer). Subunits can be diverse (different types) by alternative splicing Specificity of binding depends on the combination of alpha and beta subunits For example Cells with alpha-6, beta-4 integrins have hemidesmosomes. Bind matrix proteins in the basal lamina (like laminins) and intermediate filaments, like keratins, in the cytoplasm White blood cells have alpha1 and beta 2 integrins that bind to endothelial cells. Macrophages have alpham and beta 2 integrins that also bind to endothelial cells. Platelets have beta 3 subunit in their integrins that allows them to bind fibrinogen during blood clotting. Humans with Glanzmann’s disease are genetically deficient in beta 3 containing integrins. These patients bleed excessively Cells with alpha 5 and beta 1 integrins bind fibronectin in the extracellular matrix.
Notes
2.102
© Copy Right: Rai University
71
