Specializations of Basal and Lateral Cell Surface

Question 1

What are Tight Junctions?

Answer 1

1. Join together cytoskeleton of adjacent cells
2. Claudin Occludins
   * Associated Membrane proteins
3. Seal
   * Interactions between Transmembrane proteins Claudin and Occludin
4. Developed

• Blood-brain barrier
• Small intestines (prevent macromolecules from digestion)

5. Ex:

• Receptor-mediated Endocytosis
• Exocytosis at basolateral surface

Question 2

What are Medical Significance of Tight Junctions?

Answer 2

1. Disruption of Tight Junctions

• Food Poisoning
  
  • Enterotoxin produced by Clostridium perfringens
  • Binds to Claudin molecules and breakdown tight junctions
• Duodenal Ulcer
  
  • Helicobacter pylori (H. Pylori) translocated to duodenum causing disruption of tight junction
  • Leads to injury of mucosa and ulcer
• Asthma Attack
  
  • Dust mite inhaled with dust particles, Peptidases cleaves Occludins
  • Breaksdown tight junctions in respiratory epithelium
  • Initiates immune response

Question 3

Question 4

What are Zonula Adherens?

Answer 4

1. Type of Adherent (Anchoring) Junctions
2. Contains

• E-CADHERIN
  
  • Mediates Cell Adhesion

3. Intracytoplasmic ends

• Binds CATENIN
  
  • Linked via VINCULIN, ALPHA-ACTININ TO ACTIN FILAMENTS OF CYTOSKELETON

4. Extracytoplasmic ends

• Binds Extracytoplasmic ends of E-CADHERINS
• In the presence of Calcium

*Removal of Calcium disrupts Junction and loss of E-cadherin

• Loss of E-cadherin in cancer tumors promotes Metastases

Question 5

What are Desmosomes or Macula Adherens?

Answer 5

1. Contains

• Desmoglein
• Desmocollin (Ca dependent; E-cadherins)
• Desmoplakin protein
• Plakoglobin protein
• Keratin filaments

2. Resist Shearing Force
3. Found

• Simple squamous epithelium
• Stratified squamous epithelium
• Muscle tissue

Question 6

What diseases are involved with Desmosomes or Macula Adherens?

Answer 6

1. Arrhythmogenic Right Ventricular Dysplasia
   * Mutation in gene coding PLAKOGLOBIN (linking protein; E-cadherin to cytoskeleton
2. Pemphigus

• Blister Disease
• Anti-desmoglein IgG autoantibodies
  
  • Disrupts desmosomes that link with skin epithelial

3. Bullous Impetigo

• Exfoliative toxins of Staphylococcus aurueus
• Target DESMOGLEIN
• No redness
• Itching
• Fluid-filled

Question 7

What are Gap Junctions?

Answer 7

1. Composed of TWO CONNEXONS (Hemichannels)
2. Connexon

• Assembly of 6 Transmembrane proteins called Connexin
• Hydrophilic pore

3. Opening and closing depends of Calcium concentration
4. Found in all cells Except Mobile cell types (Sperm and erythrocytes)
5. Function

• Retina
  
  • Adaption of light
• Heart and Visceral Muscle
  
  • Produce Rhythmic Contraction

6. Mutation

• CHARCOT-MARIE-TOOTH DISEASE
  
  • Connexin mutation
  • Abnormal neuronal migration in the Cerebral Cortex
  • Deafness

Question 8

What are Hemidesmosomes?

Answer 8

1. Basal Lamina
2. Half-desmosomes
   * Connect Basal Domain of epithelial cells to underlying basal lamina
3. Consist
   * Attachment plaque on cytoplasmic side of basal plasma
4. Integrins

• Intracellular domain
  
  • Binds to Keratin intermediate filaments
• Extracellular domain
  
  • Binds to Laminin protein and type IV Collagen

Question 9

What diseases are involved with Hemidesmosomes?

Answer 9

1. Bullous Pemphigoid

• Subepidermal
• Autoimmune
• Blistering disease
• IgG autoantibodies bind to skins basement membrane
• Inflammatory cells release Proteases
  
  • Degrade hemidesmosomal proteins leading to blistering

2. Clinical representation

• Tense bullae
• Affects elderly (5th to 7th decade of life)

Question 10

What is the Basement Membrane?

Answer 10

1. Non-cellular form of extracellular matrix
2. Not visible by LM with H and E stain
3. Visible

• Periodic Acid Schiff (PAS) stain
  
  • In Kidney glomerulus and lung alveoli
• Silver Stain
  
  • Reveals Reticular Fibers

Question 11

What is Basement Membrane Comprised of?

Answer 11

1. Basal Lamina

• 20-100 nm thick
• Consist
  
  • Lamina Lucida
    
    • ELECTROLUCENT
    • Glycoprotein: LAMININ
  • Lamina Densa
    
    • ELECTRODENSE
    • Collagen Type IV (coated w/ heparan sulfate proteoglycan perlecan)
• Laminin and Type IV collagen held together by ENTACTIN/NIDOGEN and Proteoglycan: PERLECAN

2. Lamina Reticularis

• Contains Reticular fibers (Type III Collagen)
• Bound to Basal Lamina
  
  • By Anchoring fibrils of Type VII Collagen

*Both visible with TEM

Question 12

What is the Function of Basal Lamina?

Answer 12

1. Structural support and Polarity to Epithelial Cells
2. Maintain cell shape and cell adhesion
3. Filtration
   * Filters blood plasma to become urine
4. Regeneration
   * Wound healing