Cell Junctions and ECM Notes

Cell Junctions and the Extracellular Matrix

Overview of Cell Junctions (p1105-1108)

  • Cell junctions: Binding of cells to each other and/or to the extracellular matrix (ECM).
  • Three broad categories:
    • Occluding junctions: Seal cells together as a sheet.
    • Communication junctions: Allow molecules to pass between adjacent cells.
    • Anchoring junctions: Mechanically hold cells together or to the extracellular matrix. (Main focus)

Occluding Junctions (p1116-1120)

Tight Junctions and the Organization of Epithelia
  • Tight junctions form a seal between cells and a fence between plasma membrane domains.
  • Occluding junctions form a selective permeability barrier across epithelial cell sheets.
  • Tight junctions are formed near the apical surface between adjacent epithelial cells (Figure 19-18).
  • A dark dye injected into the bloodstream cannot pass the tight junction (Figure 19-19).
  • Tight junctions contain strands of transmembrane adhesion proteins (claudins and occludins) (Figure 19-20 and 19-21).
  • These proteins prevent the lateral diffusion of substances between cells.

Communicating Junctions (p1121-1123)

Gap Junctions
  • Gap junctions form cell-to-cell channels that allow the passage of molecules that are 1000 daltons or less (Figure 19-24).
  • Molecular mass cut-off determined by injecting fluorescent dyes of different masses.
  • Critical functions:
    • Allow cells to share metabolites.
    • Promote electrical coupling of adjacent cells.
Gap-Junction Connexon
  • Connexins are the proteins that constitute gap junctions.
  • Twelve connexin proteins, six in each cell, form a cell-to-cell channel termed a connexon (Figure 19-25).

Anchoring Junctions

  • Connect the cytoskeleton of a cell either to the cytoskeleton of its neighbors or to the extracellular matrix.
  • Four categories: Adherens, Desmosomes, Hemi-desmosomes, and Focal Adhesions (Actin-linked Cell-Matrix junctions) (Table 19-1, Figures 19-2, 19-3).
  • Form mechanically strong connections.
  • Constituents:
    • Transmembrane protein forming cell-to-cell or cell-to-ECM connections.
    • Accessory proteins linking the membrane protein to the cytoskeleton.
Adherens Junctions (p1113)
  • Respond to tension generated from inside and outside the tissue.
  • Adhesion belt: Parallel rings of actin underlie the plasma membrane (Figure 19-13).
  • Actin is attached to transmembrane proteins called cadherins via anchoring proteins such as catenin, vinculin, and α-actinin.
  • Cadherins from one cell bind to cadherins in adjacent cells.
Tissue Remodeling (p1114)
  • Depends on the coordination of actin-mediated contraction with cell-cell adhesion.
  • Contraction of actin filaments in adherens junctions forms epithelial tubes during development.
Desmosomes (p1116)
  • Promote cell-to-cell interactions.
  • Cytoskeleton component: Intermediate filaments rather than actin filaments (Figure 19-16).
  • Intermediate filaments are bound to a cytoplasmic plaque composed of proteins including plakoglobin and desmoplakin.
  • These proteins connect the cytoskeleton to cadherin, similar to adherens junctions.
Integrins (p1151)
  • Transmembrane proteins connecting animal cells to the extracellular matrix.
  • Form anchoring junctions that bind cells to the ECM.
Hemi-desmosomes
  • Link integrins to intermediate filaments.
  • Form strong junctions that help maintain the integrity of tissues by forming a strong adhesion of cell to ECM (Figure 19-57).
Focal Adhesions
  • Junctions in which integrins are linked to actin filaments on the inside of the cell.
  • More dynamic than hemi-desmosomes.
  • Account for more transient interactions between cells and the ECM, e.g., in motile cells during cell migration.
  • Important during development.

CADHERINS AND CELL-CELL ADHESION (p1108)

  • Cadherins promote cell-to-cell binding.
  • Require Ca2+Ca^{2+} ions for their activity (Figure 19-6B).
  • Cadherins Mediate Homophilic Adhesion (p1108)
  • Exhibit homophilic binding (Figure 19-5, top).
  • Different cell types expressing different cadherins sort out according to the cadherin they express (Figure 19-9).
  • Cadherin-dependent Cell-Cell Adhesion guides the Organization of developing Tissues (p1110)
  • Cell-Cell Junctions Send Signals to the Cell Interior.
  • Cell-Cell (and Cell-ECM) junctions can initiate signaling pathways inside the cell, impacting cell division and cell survival versus apoptosis.

THE EXTRACELLULAR MATRIX OF ANIMALS (p1127)

  • Cells of multicellular animals are usually found within a meshwork of extracellular proteins and carbohydrates termed the extracellular matrix (ECM).
  • The Extracellular Matrix Is Made and Oriented by the Cells Within It (p1128)
  • Cells synthesize and secrete the proteins and carbohydrates that constitute the ECM.
  • Cells become embedded in the ECM components that they have secreted.

Glycosaminoglycan (GAG) Chains (p1129)

  • Carbohydrates are a major component of the ECM.
  • Glycosaminoglycans (GAGs) are long, unbranched polysaccharide chains composed of repeating disaccharide units (Figure 19-31, 19-35, 19-36).
  • Contain many negative charges, attracting cations and water to form a hydrated gel.
  • The gel-like texture provides resistance to compression.
Hyaluronate (p1129)
  • Present in connective tissues, resisting compression forces.
  • Example: Cartilage pads resist bone forces.
Proteoglycans (p1130)
  • Most GAGs are attached to a core protein in the Golgi, then secreted (Figure 19-35, 19-36).
  • Aggrecan's mass is mostly carbohydrate.
  • Roles:
    • Hydrated gel for cushioning.
    • Cell signaling by binding and regulating secreted proteins and signaling molecules.

Collagens (p1132)

  • Major proteins of the extracellular matrix.
  • Fibrillar collagens form fibers.
  • Three collagen polypeptides associate to form a triple helix (Figure 19-38).
  • Every third amino acid is a glycine residue, enabling helix packing.
  • Table 19-2 describes various types of collagens.
Post-Translational Modifications
  • Procollagen molecules are post-translationally modified: proline and lysine may be hydroxylated, and procollagen may be glycosylated.
  • Move through the secretory pathway (Chapter 13).
  • First made as preprocollagen; SRP sequence is cleaved to generate procollagen in the ER lumen.
  • Procollagen associates to form a triple helix; extension peptides prevent intracellular fiber formation.
  • Hydroxyl-proline and hydroxyl-lysine residues promote triple-helix stability via inter-chain hydrogen bonds.
  • Extracellular enzymes cleave extension peptides after secretion, allowing association into fibrils and fibers.

Fibronectin (p1138)

  • Protein in the ECM that binds to many other ECM components and cell surface receptors.
  • Serves as an organizer and connector of the ECM (Figure 19-47).
  • Contains domains that recognize different components in the ECM and on the cell surface.
Fibronectin Binds to Integrins (p1139)
  • The RGD (Arg, Gly, Asp) motif is the part of fibronectin that binds to integrin.
  • Peptides secreted by cancer cells can disrupt these interactions, allowing the cancer cell to detach from the ECM and migrate.

The Basal Lamina (p1141)

  • Specialized type of connective tissue or Basement Membrane .
  • Separates cells from adjacent connective tissues, e.g., underneath epithelial cell sheets.

Cell Degradation of Matrix (p1144)

  • ECM must be partially degraded for certain cells to migrate through it.
  • Matrix proteases and serine proteases carry out this function.
  • The ability of cells to degrade ECM is restricted to a few cell types in adults.
  • Cancer cells can increase secretion of matrix proteases to migrate.

INTEGRINS AND CELL-MATRIX ADHESION (p1147)

  • Integrins are involved in forming anchoring junctions between cells and the basal lamina.
  • Integrins function as sensors between the cytoplasm of cells and their extracellular environment.
  • Integrins Are Transmembrane Heterodimers That Link the ECM to the Cytoskeleton (p1147)
  • Integrins have two subunits termed α and β (Figure 19-56).
  • Different α subunits can interact with different β subunits.
  • Integrins Can Switch Between an Active and an Inactive Conformation (p1149)
  • Binding of integrin to an extracellular component causes a conformational change in the integrin so that it interacts with cytoplasmic proteins such as talin, α-actinin, and filamin.
  • These proteins undergo conformational changes that cause them to interact with cytoskeletal components such as actin.
  • Integrins Cluster to Form Strong Adhesion (p1151).

Extracellular Matrix Attachments (p1151)

  • Act Through Integrins to Control Cell Proliferation and Survival.