Cell Junctions and Tissues

• Cell junctions allow cells to contact neighboring cells, and the extracellular matrix
• Cell junctions consist of multiprotein complexes

Cell Junction Function

• Cell junctions bond cells together
• Cell junctions reduce stress placed upon cells
• Cell junctions build up the paracellular barrier of epithelia
• Cell junctions control paracellular transport
• Cell junctions enable communication between neighboring cells
• Cell junctions adhere cells to the extracellular matrix

Tissues

• A tissue is an assembly of similar cells from the same origin, working together, carrying out specific functions
• Some cell types, such as blood and immune system cells, move freely in the body
• Other cells are packed into tight communities
• Organs are formed by the functional grouping of multiple types of tissues

Epithelial Tissue

• Epithelial tissue covers body surfaces, lines body cavities, and hollow organs
• Epithelial tissue functions include protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception
• Cells are tightly bound together into sheets called epithelia
• Cell-cell junctions attach cells to each other
• Cell-matrix junctions anchor cells onto the basal lamina

Connective Tissue

• In connective tissues, the extracellular matrix (ECM) consists of macromolecules produced by cells, primarily fibroblasts, that are sparsely distributed in the interstitial matrix
• The macromolecules in the interstitial matrix, rather than the cells (fibroblasts) themselves, primarily bear mechanical stress
• Direct attachments between cells are rare
• Epithelial tissue cells attach to the connective tissue through cell-matrix junctions in the ECM

Types of Cell Junctions

• There are two main types of cell junctions: cell-cell junctions and cell-matrix junctions

Types of Cell-Cell Junctions:

• Tight junctions
• Cell-cell anchoring junctions
  • Adherens junctions
  • Desmosomes
• Gap junctions (communicating junctions/channel-forming junctions)

Types of Cell-Matrix Junctions:

• Cell-matrix anchoring junctions
  • Actin-linked cell-matrix junctions
  • Hemidesmosomes

Junctional Complex

• The junctional complex is located at the apex of the lateral membrane of polarized epithelial cells
• Involves:
  • Regulating cell-cell adhesion
  • Paracellular permeability
  • Cell polarity

Cell-Cell Junctions

Tight Junctions

• Tight junctions (zonula occludens or occluding junctions) seal the gap between epithelial cells
• They seal the intercellular space from the luminal environment
• The seal is not absolute and acts as a diffusion barrier
• Tight junctions are impermeable to macromolecules, but permeability varies for ions and small molecules
• They serve as selective permeability barriers for paracellular transport
• Usually located at the apical location and found in epithelial cells, such as lining the intestinal mucosa, urinary bladder, and respiratory tract
• Claudin and occludin are the proteins that make up tight junctions
• Tight junction disruption in the intestine causes a leaky gut, associated with the pathogenesis and progression of gastrointestinal diseases

Cell-Cell Anchoring Junctions

• Cell-cell anchoring junctions (adherens junctions and desmosomes) hold cells together
• The lipid bilayer is flimsy, and it cannot transmit large forces from cell to cell by itself
• Functionally different forms:
  • Adherens junctions
  • Desmosomes
• These junctions hold cells together and are formed by transmembrane adhesion proteins in the cadherin family (calcium-dependent adhesive proteins)
• Anchoring junctions are strong, membrane-spanning structures, tethered inside the cell to the tension-bearing filaments of the cytoskeleton
• They are widely distributed in animal tissues and are abundant in tissues subjected to severe mechanical stress, such as the heart, skeletal muscle, and epidermis
• Cell-cell anchoring junctions depend on transmembrane adhesion proteins

Cadherins

• Calcium-dependent adhesion
• Cadherins depend on extracellular Ca2+ to rigidify the extracellular domains and enable trans junctional homophilic interactions
• Removal of calcium abolishes adhesive activity and renders cadherins vulnerable to proteases
• Cadherins span the plasma membrane, one end linking to the cytoskeleton, and the other end linking to structures outside the cell

Adherens Junctions

• Adherens junctions (zonula adherens, intermediate junction, "belt desmosome" or adhesion belt) connect one actin filament bundle in one cell with that in the next cell
• Cell Junctions provide an anchorage site for the cytoskeleton
• They help to model shape of multicellular structures
• Guide the organization of developing tissues, and help construct vertebrate nervous system
• Located more basal than tight junctions, and Found in most epithelial and endothelial tissues

Desmosomes

• Desmosomes (macula adherens) connect intermediate filaments in one cell to intermediate filaments from the adjacent cell
• Provide anchorage site for cytoskeleton
• Structurally similar to adherens junctions but contain specialized proteins (desmogleins) that link with intermediate filaments instead of actin
• Provide mechanical strength
• Located in tissues that suffer from a lot of stress or stretch, such as skin muscles, intestines, stomach, and urinary bladder

Gap Junctions

• Gap junctions allow the passage of small hydrophilic molecules from cell to cell without passing through the plasma membrane
• Examples of passing molecules through gap junctions are: ions, glucose and second messengers
• The gap between cells is narrow (2-4 nm)
• Important in tissues containing electrically excitable cells
• Action potentials can spread rapidly
• Examples of gap junction usage: cardiac contraction and peristaltic movements of intestines
• Located in epithelial tissues, cardiac muscles, and smooth muscles

Cell-Matrix Junctions

• Cell-matrix anchoring junctions connects the cell to the extracellular matrix
• They depend on integrins (transmembrane proteins) bridging cell-matrix interactions
• Cell-matrix anchoring junctions sense and respond to mechanical forces acting across the junction

Integrins

• Integrins activate after binding intracellular activator proteins and produce intracellular signals that can influence almost any aspects of cell behavior
  • embryonic development
  • signaling
  • proliferation
  • survival
  • migration
  • blood clotting

Actin-Linked Cell Matrix Junctions

• Actin-linked cell-matrix junctions (focal adhesion) anchor actin filaments in cells to the extracellular matrix
• Actin-linked cell matrix junctions can be small, transient, large, and durable

Hemidesmosomes

• Hemidesmosomes anchor intermediate filaments in a cell, to the cell's extracellular matrix
• They are similar in form to desmosomes
• Hemidesmosomes use integrins instead of desmogleins to facilitate a stable adhesion of the basal side of the epithelial cells to the basement membrane (ECM)