Updated: 3/7/2019

Cell Surface Proteins

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Overview
  •  Purpose This illustration highlights the basic various types of cell-cell adhesion protein
    • 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 This illustration highlights the major types of cell junction proteins
    • 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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