U01.11.056 Epithelial cell junctions

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Learning Objectives

Analyze the molecular architecture of epithelial cell junctions and their role in maintaining tissue integrity. Master the specific proteins (claudins, cadherins, connexons, integrins) and their associated clinical pathologies, particularly the blistering diseases linked to desmosomes and hemidesmosomes.

1. Intercellular Junctions (Cell-to-Cell)

Epithelial cells are organized with distinct apical-basal polarity. The junctions between adjacent cells ensure barrier function, mechanical strength, and communication.

Junction Type Key Proteins Function & High-Yield Detail
Tight Junction (Zonula Occludens) Claudins, Occludins Prevents paracellular movement of solutes. Located at the most apical point.
Adherens Junction (Zonula Adherens) Cadherins (Ca2+-dependent) Connects actin cytoskeletons. Loss of E-cadherin promotes metastasis in cancer.
Desmosome (Macula Adherens) Desmogleins Structural support via intermediate filaments (cytokeratin). Target in Pemphigus Vulgaris.
Gap Junction Connexons Channels permit electrical and chemical communication between cells.

2. Cell-to-Matrix Junctions (Basal)

These junctions anchor the epithelial layer to the underlying basement membrane and extracellular matrix (ECM).

  • Hemidesmosome: Connects keratin (intermediate filaments) in basal cells to the underlying basement membrane. Autoantibodies against these lead to Bullous Pemphigoid.
  • Integrins: Transmembrane proteins that bind to collagen, laminin, and fibronectin in the basement membrane to maintain basolateral integrity.

Activity: Blistering Disease Differential Table

Disease Molecular Target Clinical Finding
Pemphigus Vulgaris Desmosomes (Desmoglein) Flaccid bullae; Positive Nikolsky sign; Intraepidermal.
Bullous Pemphigoid Hemidesmosomes Tense bullae; Negative Nikolsky sign; Subepidermal.

Activity: Apical to Basal Sequence Challenge

High-Yield Mnemonics:

  • Hemidesmosomes: They are down “Bullow” (Bullous Pemphigoid).
  • Adherens: Adherens = Actin.
  • Cadherins: Cadherins are Calcium-dependent.

Activity: