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