BIO345 Chapter 7

• PM constitutes the boundary between a cell and its environment. However, cells interact with each other and with their extracellular environment
• These interactions regulate diverse activities (cell migration, cell growth and differentiation) and determine the 3D organization of tissues and organs during development

  
• Cells are organized into tissues
• In the skin, the cells of the epidermis adhere to each other by specialized contacts
• The basal layer of epidermal cells adheres to a noncellular layer: the basement membrane
• The dermis consists of extracellular elements that interact with each other and with the receptors located at the surfaces of fibroblasts
• The ECM of Epithelia plays a pivotal role in controlling cell behavior, supporting cell collectives with both biochemical information, and providing a correct mechanical environment
• Cell-cell and cell-ECM interactions


  Achieved via "adhesion molecules"

  
• Cell-adhesion molecules (CAMs) are tightly controlled in time and space to correctly determine the structures and functions of tissues, and provide essential communication between cells and their environment
• Families of cell-adhesion molecules

  • Cadherins
  • Selectins
  • Immunoglobulin superfamily (Ig-SF)
  • Integrins

  
• Cadherins


  Transmembrane proteins that mediate intercellular adhesion between structural cells (epithelial and endothelial cells)

  
• Cadherins are involved in maintaining tissue integrity, cell-cell recognition, signaling, communication, growth, and angiogenesis

  
• Cadherins


  Are calcium-dependent adhesion molecules
• Cells expressing one type of cadherin preferentially adhered to other cells expressing the same cadherin
• Classical cadherins


  • Contain a large extracellular segment consisting of five tandem domains of similar size and structure, a single transmembrane segment, and a small cytoplasmic domain
  • The cytoplasmic domain is associated with cytosolic proteins, having a dual role: they tie cadherins to cytoskeleton and they transmit signals to the cytoplasm and nucleus

  
• Ca2+ form bridges between the successive domains maintaining the rigidity of extracellular domain of cadherin required for cell adhesion

  
• Cell adhesion results from the interaction between the extracellular domains from opposing cells to form a "cell-adhesion zipper"

  
• Cadherin loss play a key role in the spread of malignant tumors (a major hallmark of epithelial-mesenchymal transition)
• Epithelial-mesenchymal transition


  A biologic process that allows a polarized epithelial cell, which normally interacts with basement membrane via its basal surface, to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype, which includes enhanced migratory capacity

  
• Ca2+-dependent adhesive junctions give rigidity to tissues (i.e., epithelia and cardiac muscle are difficult to separate)
• Types of cell-cell adhesive junctions

  • Adherens junctions
  • Desmosomes

  
• Adherens junctions


  Form a continuous belt near the apex of epithelial cells helping in cell binding to its neighbors: zonulae adherens

  
• Adherens junctions assembly


  1. Two unattached epithelial cell precursors explore their surroundings with membrane extensions

  2. When cells get in contact, small cadherin and catenin clusters form at the contact sites and associate with actin, leading to activation of the small monomeric GTPase Rac, an important actin regulator

  3. Rac promotes additional actin projections and thereby promoting further recruitment of cadherins and their associated catenin proteins

  4. Actin remodeling toward the assembly of linear, contractile filament bundles

  5. Assembly of myosin II filaments that associate with bundles of actin filaments to generate contractile activity

  
• Desmosomes


  Disk-shaped adhesive junctions of ~ 1 μm diameter, particularly found in tissues that are subjected to mechanical stress: cardiac muscle and the epithelial layers of the skin and uterine cervix
• Desmosomes in keratinocytes are resistant to disruption by chelation of extracellular calcium. It has been suggested that this represents a hyper-adhesive state of these intercellular junctions that is crucial for the maintenance of epidermal integrity
• Selectins


  Integral membrane glycoproteins that recognize and bind to a particular arrangement of sugars in the oligosaccharides projecting from the surfaces of other cells

  
• Types of selectins


  • E-selectin (present on endothelial cells)
  • P-selectin (present on platelets and endothelial cells)
  • L-selectin (present on leukocytes)
• Selectins mediate transient interactions between circulating leukocytes and vessel walls at sites of inflammation and clotting

  
• Capturing a leukocyte is a challenging task because these cells are flowing through the bloodstream at a considerable speed
• Selectins are well-suited for this function because selectin–ligand interaction becomes stronger with increasing pulling forces (when the leukocyte is being pulled away from a given site on the vessel wall)
• Immunoglobulin Superfamily (Ig-SF)


  Immunoglobulins (or Ig) consist of polypeptide chains composed of a number of similar domains, each of which is composed of 70 to 110 amino acids organized into a tightly folded structure

  
• Members of the Ig-SF are involved in various aspects of immune function and mediate Ca2+ independent cell–cell adhesion
• Most Igs mediate the specific interactions of lymphocytes with cells required for an immune response (macrophages, other lymphocytes, and target cells)
• Some IgSF members mediate adhesion between nonimmune cells, such as vascular cell-adhesion molecule (VCAM), neural cell-adhesion molecule (such as NCAM and L1)
• NCAM and L1 play important roles in nerve outgrowth, synapse formation, during the development of the nervous system
• Mutations in the L1 gene can have devastating consequences, such as babies being born with a deadly condition of hydrocephalus (abnormal buildup of cerebrospinal fluid in the ventricles)
• Integrins


  Found only in animals and humans, heterodimers composed of two noncovalently linked membrane-spanning polypeptide chains (α and β)
• Intercellular adhesion molecule (ICAM) is expressed by several cell types, including leukocytes and endothelial cells

  
• Immunoglobulin Superfamily (Ig-SF)


  Some IgSF members mediate adhesion between nonimmune cells. Ex. vascular cell-adhesion molecule (VCAM), neural cell-adhesion molecule (such as NCAM and L1)

  
• NCAM and L1


  • Play important roles in nerve outgrowth, synapse formation, during the development of the nervous system