Lecture 5: CAMs And Junctional Complexes

Question 1

Describe the basement membrane, including it’s purpose, components, and approximate size.

Answer 1

Basement Membrane consists of the Epithelial Basal Lamina, and the connective Reticular Lamina, which form together to separate epithelial tissue from connective tissue. It is approximately 50-80 nm thick.

Question 2

What are some of the components that make up the basal lamina, and the reticular lamina

Answer 2

Reticular Lamina - Type III collagen (aka Reticular Fibers)

Basal Lamina - Laminin, Fibronectin, Type IV collagen, Heparan Sulfate Proteoglycans, and Nidogen (also called entactin)
See Fig 1-21 for tissue sample of basement membrane

Question 3

Briefly describe Type IV collagen

Answer 3

Does Not form fibrils, and is produced by epithelial cells, which seems to be the main thing that sets it apart from other collagen

Question 4

Briefly describe laminins

Answer 4

Primary “Unit” of the basal lamina; has 3 chains: Alpha, Beta, and Gamma
Laminin has binding sites for three other components of the basal lamina (Proteoglycans, Type IV collagen, and entactin) as well as Integrin

Question 5

Briefly Describe Fibronectin

Answer 5

Fibronectin is made of 2 Polypeptide Chains, connected by Disulfide Bonds. Fibronectin has 2 potential forms: Cellular (Produced by fibroblasts), and Plasma (Secreted into blood by hepatocytes)

Fibronectin has binding sites for integrin, heparin, collagen, and fibrin.

Question 6

List the 4 main types of Calcium Adhesion Mollecules, whether or not they’re calcium dependent, what types of ligands they bind to, and their Junction Types

Answer 6

1. Cadherins - Yes - Other Cadherins - Occludens and Desmosomes
2. Selectins - Yes - Carbohydrates - None
3. Integrins - No - Extracellular Matrix Molecules - Hemidesmosomes
4. Ig Superfamily - No - Integrins - None

Question 7

Describe Cadherins, including their 3 Classical Types, and nonclassical cadherins.

Answer 7

• Type of adheren reliant on calcium usually found in cis/trans homophilic dimers. This includes E-Cadherins (Found in Epithelial Cells), N-Cadherins (in Nerve Cells), and P-Cadherins (Placenta)
• Nonclassical Cadherins include desmocollins, desmogleins, and are found in desmosomes (macular adherens)

Question 8

Describe E-Cadherins

Answer 8

• Epithelial Cadherins are the most common types of cadherins. - They form HVA dimers for binding faces (amino acid chain combination) at the tips of the extracellular end of their molecules and facilitate cis-homophilic dimers with calcium ions.
• Loss of E-Cadherins is associated with invasive tumor cells

Question 9

Describe the proteins that are known to bond the cytoplasmic end of cadherins with the cell’s cytoplasmic actin

Answer 9

Catenins: There are 3 known components of catenin:

• Beta and plakoglobin catenins: Attach to the cytoplasmic end of cadherins. The beta catenin is also known to be a transcription cofactor and binds to the alpha catenin.
• Alpha Catenins - bind directly to the cytoplasmic actin.

Question 10

Figure 1-8 Quiz:

1. What forms when two cadherin dimers join?
2. How many domains are there in the extracellular portion of cadherin for calcium?
3. What are the three actin binding proteins used alongside catenin?

Answer 10

1. 2 cis-homophilic dimers join to form a trans-homophilic interaction
2. 4
3. Fibrin-1, Vinculin, and Alpha-Actinin

Question 11

Briefly describe the function of selectin

Answer 11

1. Binds to carbohydrate molecules (things that do this are lectins)
2. The binding site for selectin is called a CRD (carb receptor domain) and is calcium-dependent
3. Involved in the movement of leukocytes from blood to tissues

Question 12

Describe the 3 types of selectins and their relation to immunological inflammation

Answer 12

1. L-Selectins - Carried by LYMPHocytes to sulfated carbohydrates
2. E-Selectins - Expressed by ENDOthelial cells
3. P-Selectins - Expressed by PLATELETS AND activated endothelial cells.
   Selectins and Integrins are play a significant role in Homing Lymphocytes to Inflamed Areas

Question 13

Describe Integrins

Answer 13

While adherins are responsible for cell-cell adhesing, integrins are responsible for bonding cells to extracellular related materials, such as fibronectin and laminin.

• Extends from the cytoskeleton into the extracellular matrix
• Consists of 17 possible alpha subunits, and 8 possible beta subunits

Question 14

1. What is the amino sequence used to bind integrin with fibronectin and laminin?
2. What does the laminin and fibronectin in the basement membrane usually bind to?
3. What are integrin’s role in hemidesmosomes?

Answer 14

1. RGD (Arginine, Glycine, Aspartic Acid)
2. Type IV Collagen, Entactin, and proteoglycans
3. In hemidesmosomes, integrins link the basal domain of cells to the extracellular matrix through intracellular tonofilaments (Such as keratin)

Question 15

What are the 3 binding proteins associated with binding actin with integrins in the cytoplasm?

Answer 15

Talin, vinculin, and alpha-actinin

Question 16

Briefly describe the process of a lymphocyte/neutrophil homing in on inflamed sites (specifying the roles of selectins and integrins)

Answer 16

1. Lymphocytes travel through vascular endothelium by “rolling” along the cell walls.
2. Selectins along the epithelial cells lining bind to lymphocyte carbohydrate ligands, slowing the roll. If activated, it also triggers chemical mediators (ICAMs) that activate more ligands, and helps Integrin further bind to the lymphocyte.
3. The integrin works with actins to interact with the ligands on the cell, mediating the cell to be “pushed” through the endothelial lining.

Question 17

Describe the characteristics of the Immunoglobulin superfamily

Answer 17

• Members of this family possess an extracellular segment with one or more domains characteristic of Immunoglobulins.
• 2 (3) types of this family include N-CAMs, which mediates homophilic and heterophilic interactions.
  And ICAMs (Types I and II), which facilitate transendothelial migrations of leukocytes.