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Updated: Mar 7 2019

Cell Surface Proteins

  • Overview
    • Purpose
      • allow cells to attach to each other
        • via different types of cell-cell junctions
      • allow cells to attach to the basement membrane
        • complex interaction between cells and supporting matrix
        • two divisions
          • basal lamina - provides attachment for most types of epithelium
            • composition
              • type IV collagen
              • laminin
              • heparan sulfate
          • reticular lamina - supports lymphoid and adipose tissues
            • composition
              • type III collagen (reticular fibers)
    • Types of molecules
      • cadherin
        • structure
          • calcium dependent
          • binds cadherin dimer on another cell extracellularly
          • binds actin intracellularly (via catenin)
        • function
          • ↑ cell-cell binding
            • cadherin receptor ↓ regulated in cancer metastasis
      • selectin
        • calcium dependent
        • function
          • binds carbohydrates in cell-cell interactions
        • subtypes
          • L-selectin
            • on leukocytes
            • L-selectins have Sialyl-Lewis glycoproteins as ligands
          • P-selectin
            • on platelets and endothelial cells
          • E-selectin
            • on endothelial cells
            • binds leukocytes strongly
              • ↑ expression on surface during acute inflammatory response
                • stimulated by TNF-α
          • LAD II is caused by a defective selectin ligand
            • impaired interaction with E- and P- selectins on endothelium
              • causes a rolling defect
              • presents with recurrent bacterial infections with psychomotor and mental retardation
      • integrin
        • structure
          • calcium-independent
          • transmembrane
          • binds fibronectin and laminin extracellularly
          • binds actin intracellularly
        • function
          • binds leukocytes
            • neutrophilic attachment in adhesion via an integrin LFA-1
            • defective in leukocyte adhesion deficiency (LAD) type I
              • interaction with ICAM and VCAM impaired
              • causes an adhesion defect
              • presents with recurrent bacterial infections and delayed loss of umbilicus postpartum
          • bind to laminin in ECM
            • integrin receptor ↑ regulated in cancer metastasis
  • Types of Cell-Cell Junctions
    • Tight junctions
      • aka zonula occludens
      • structure
        • zona occuldens (ZOs) 1, 2, 3
        • claudin proteins
        • membrane spanning proteins
          • bind cellA actin intracellularly on one end
          • bind cellB actin intracellularly on opposite end
      • location
        • apical end of epithelial cells
      • function
        • prevent diffusion
        • create cell membrane polarity
    • Adherens junctions
      • aka zonula adherens
      • structure
        • cadherin proteins
          • Ca2+-dependent adherin = cadherin
      • location
        • belt around cell
          • below tight junction
    • Desmosomes
      • aka macula adherens
      • structure
        • cadherin proteins
          • link between two cells
          • attach to intermediate filaments
        • keratin and desmoplakin proteins
      • location
        • distinct sites
      • function
        • rivets
        • gives strength to junction between cells
      • clinical importance
        • pemphigus vulgaris
          • pathophysiology
            • auto-IgG against desmosomal proteins in keratinocytes
            • type II hypersensitivity
          • presentation
            • painful, flaccid vesicles form on skin and oral mucosae
              • located above basal layer
              • because it is above the basal layer the blister is weak
                • positive Nikolsky sign
                  • outer epidermis separates with gentle rubbing
            • acantholysis
              • loss of connection between cells
            • post-inflammatory hyperpigmentation
          • treatment
            • immunosuppression (corticosteroids)
    • Hemidesmosomes
      • structure
        • composed of integrins
        • bind type IV collagen, fibronectin, laminin of basal lamina extracellularly
        • bind intermediate filaments intracellularly
      • function
        • like a desmosome but instead of attaching cell-to-cell it attaches cell-to-basement membrane
          • "half of a desmosome"
      • clinical importance
        • bullous pemphigoid
          • pathophysiology
            • auto-IgG against basement membrane hemidesmosomes
            • type II hypersensitivity
            • can be drug-induced
          • presentation
            • wide distribution of skin blisters
              • unlike pemphigus vulgaris → does not involve oral mucosae
              • vesicles below the epidermis
              • stronger vesicles
                • negative Nikolsky sign
            • NO acantholysis
          • treatment
            • immunosuppression (corticosteroids)
        • cancer
          • metastasis involves timely ↓ regulation of hemidesmosomal proteins
    • Gap junctions
      • structure
        • pores formed by 6 connexon proteins
      • function
        • allow direct passage of small molecules from one cell to another
          • e.g. Ca2+, cAMP
        • role in electrical and metabolic signalling
        • no role in strength
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