WEEK 10 (Basement membranes and junctions between epithelial cells)

Question 1

What are the characteristics of the shapes, sizes & nuclei of Epithelial cells?

Answer 1

• Shapes vary from COLUMNAR, CUBOIDAL & LOW SQUAMOUS CELLS
• Cells’ size and shape are dictated by their function and nuclear shape corresponds to cell shape
• Nuclei can be ELLIPTIC (oval), SPHERICAL or FLATTENED
• COLUMNAR CELLS = ELONGATED NUCLEI
• SQUAMOUS CELLS = FLATTENED NUCLEI
• CUBOIDAL/PYRAMIDAL CELLS = SPHERICAL NUCLEI

Question 2

What does the nuclei allow to determine?

Answer 2

The number of layers in an epithelium

Question 3

Where are most epithelia found?

Answer 3

Most epithelia are found adjacent to connective tissue containing blood vessels from which the epithelial cells receive nutrients and O2

Question 4

Do epithelia contain blood vessels?

Answer 4

No

Question 5

Describe Connective tissue/Epithelia lining Organs

Answer 5

The connective tissue that underlies the Epithelia lining the organs of the digestive, respiratory and urinary systems is called the LAMINA PROPRIA. The area of contact between the two tissues is increased by SMALL EVAGINATIONS called PAPILLAE projecting from the CONNECTIVE TISSUE into the EPITHELIUM.

Question 6

What are the characteristics of Epithelial cells within the cell?

Answer 6

• Show polarity
• Organelles and membrane proteins are distributed unevenly within the cell
• Region of the cell contacting the ECM and connective tissue is called the BASAL POLE
• Opposite end of cell is called the APICAL POLE
• Regions of CUBOIDAL or COLUMNAR CELLS that adjoin neighbouring cells comprise the cells’ lateral surfaces

Question 7

What is the basement membrane?

Answer 7

A semipermeable filter for substances reaching epithelial cells from below. It is a thin extracellular, felt-like sheet of macromolecules that the basal surface of all epithelia rests on.

Question 8

What are the two parts of the basement membrane that can be seen with the TEM?

Answer 8

BASAL LAMINA
- nearest the epithelial cells
- a thin, electron-dense, sheet-like layer of fine fibrils

FIBROUS RETRICULAR LAMINA
- beneath the basal lamina
- more diffuse

Question 9

Describe what can be seen of the Basal lamina using TEM

Answer 9

The dense BASAL LAMINA may appear with thin clear zones on each side and is anchored to a thicker, more diffuse RETICULAR LAMINA containing collagen III fibers

HEMIDESMOSOMES bind the basal surface of the epithelial cell to the basal lamina

Question 10

What components does the Basal lamina include?

Answer 10

• Type IV collagen
• Laminin
• Nidogen and Perlecan
• Fibrillin microfibrils

Question 11

What is distinguishable about Type IV collagen?

Answer 11

Monomers of type IV collagen self assemble into a two-dimensional network of evenly spaced subunits resembling the mesh of a window screen

Question 12

What are the properties of Laminin?

Answer 12

• Large glycoproteins that attach to TRANSMEMBRANE INTEGRIN PROTEINS in the basal cell membrane
• Project through the mesh formed by type IV collagen

Question 13

What are the properties and functions of Nidogen and Perlecan?

Answer 13

• A short, rod-like protein and a proteoglycan
• Both cross-link LAMININS to the TYPE IV COLLAGEN NETWORK
• Helps provide the basal lamina’s 3D structure
• Binds epithelial to the structure
• Determines its POROSITY and size of molecules ale to filter through it

Question 14

What are the properties of Fibrillin?

Answer 14

• Attach the LAMINA DENSA to ELASTIC FIBERS
• Known to have elastic properties
• Mutation in the fibrillin gene (FBN1) causes Marfan’s syndrome

Question 15

Where foes the assembly of the basal lamina occur?

Answer 15

Outside the cell at its basal domain

Question 16

Describe the production of Basal Lamina

Answer 16

1) Each epithelial cell first synthesises and secretes its molecular components. The CALCIUM-DEPENDENT POLYMERISATION of laminin molecules that occurs at the basal cell surface initiates basal lamina formation
2) LAMININ POLYMERS are anchored to the cell surface by INTEGRIN RECEPTORS and at the same time TYPE IV COLLAGEN SUPRASTRUCTURE is assembled in close proximity to laminin polymers
3) These two structures are connected by ENTACTIN or NIDOGEN bridges

Question 16

Describe the production of Basal Lamina

Answer 16

1) Each epithelial cell first synthesises and secretes its molecular components. The CALCIUM-DEPENDENT POLYMERISATION of laminin molecules that occurs at the basal cell surface initiates basal lamina formation
2) LAMININ POLYMERS are anchored to the cell surface by INTEGRIN RECEPTORS and at the same time TYPE IV COLLAGEN SUPRASTRUCTURE is assembled in close proximity to laminin polymers
3) These two structures are connected by ENTACTIN or NIDOGEN bridges

Question 17

What are the properties of the Reticular lamina?

Answer 17

• Contains type III collagen
• Bound to the basal lamina by anchoring fibrils of type VII collagen

Question 18

What are the functions of the basement membrane?

Answer 18

• Help provide structural support for epithelial cells
• Attach epithelia to underlying connective tissue
• Help organise integrins & other plasma membrane proteins to maintain cell polarity and help localise endocytosis & signal transduction
• Mediate many cell-to-cell interactions
  (involving EPITHELIA and MARK ROUTES for certain cell migrations along epithelia)
• Serves as a scaffold that allows rapid epithelial repair and regeneration

Question 19

What is the importance of Gap Junctions?

Answer 19

Allows the exchange of nutrients and signal molecules between cells without loss of material into the intercellular space

Question 20

Describe Tight Junctions

Answer 20

MAJOR TRANSMEMBRANE LINK PROTEINS:
- Occludins
- Claudins
- ZO Proteins

CYTOSKELETAL COMPONENTS: Actin Filaments

MAJOR FUNCTIONS:
- Seals adjacent cells to one another
- Controls passage of molecules between them
- Separates apical and basolateral membrane domains

MEDICAL SIGNIFICANCE:
Defects in occluding may compromise the foetal blood-brain barrier leading to severe neurologic disorders

OTHER PROPERTIES:
- Appear as a band of branching strands in the membrane around each cell’s APICAL END
- Adjacent membranes appear fused in TEM
- Apical cell membranes are part of the LUMINAL COMPARTMENT of a tissue or organ
- Basolateral domains are part of basal compartment that underlies connective tissue

Question 21

Describe Adherent Junctions

Answer 21

MAJOR TRANSMEMBRANE LINK PROTEINS:
- E-Cadherin
- Catenin complexes

CYTOSKELETAL COMPONENTS: Actin Filaments

MAJOR FUNCTIONS:
- Provides points linking the cytoskeletons of adjacent cells
- Strengthens and stabilises nearby tight junctions

MEDICAL SIGNIFICANCE:
Loss of E-cadherin in epithelial cell tumours promotes tumor invasion and the shift to malignancy

OTHER PROPERTIES:
- Cell adhesion is mediated by cadherins
- Actin filaments linked to the adherent junctions form part of the “TERMINAL WEB” which is a cytoskeletal feature at the apical pole in many epithelial cells

Question 22

Describe Desmosomes

Answer 22

MAJOR TRANSMEMBRANE LINK PROTEINS:
Cadherin family proteins

CYTOSKELETAL COMPONENTS:
Intermediate filaments (Keratins)

MAJOR FUNCTION:
- Provides points of strong intermediate filament coupling between adjacent cells
- Strengthening the tissue

MEDICAL SIGNIFICANCE:
Autoimmunity against Desmoglein I leads to DYSHESIVE SKIN DISORDERS characterised bye reduced cohesion of epidermal cells

OTHER PROPERTIES:
Disc-shaped structures at the surface of one cell that are matched with identical structures at an adjacent cell surface

Question 23

Describe Hemidesmosome

Answer 23

MAJOR TRANSMEMBRANE LINK PROTEINS:
Integrins

CYTOSKELETAL COMPONENTS: Intermediate Filaments

MAJOR FUNCTIONS:
Anchors cytoskeleton to the basal lamina

MEDICAL SIGNIFICANCE:
Mutations in the integrin-B4 gene are linked to some types of EPIDERMOLYSIS BULLOSA (a skin blistering disorder)

OTHER PROPERTIES:
- Resemble a half-desmosome
- Integrins of hemidesmosomes bind primarily to laminin molecules in the basal lamina