cell junctions

Cell junctions are essential for multicellular life and play roles in tissue formation, immune cell response, and nervous system function.

• Cells interact with each other and the extracellular matrix (ECM) through various junctions that must form and release bonds as needed.

Types of Cell Junctions

1. Junctional Interactions

• Activities of cells are influenced by their relationships with other cells and the ECM.

• Understanding cell interactions improves comprehension of cellular functions.

Major Types of Junctions

1. Occluding Junctions (Tight Junctions)

   • Seal gaps between epithelial cells.

   • Prevent leakage of substances across epithelial layers.

2. Anchoring Junctions

   • Types:

     • Cell-Cell Anchoring Junctions: Connect cytoskeletons of adjacent cells.

     • Cell-ECM Anchoring Junctions: Link cytoskeleton of cells to ECM.

   • Examples:

     • Focal Adhesions: Use integrins to attach to ECM.

     • Hemidesmosomes: Anchor cells to ECM, connecting to intermediate filaments.

3. Channel-Forming Junctions (Gap Junctions)

   • Allow passage of small, water-soluble molecules between cells.

2. Tight Junctions

• Formed by transmembrane proteins that seal epithelial cells near their apex.

• Prevents materials in the gut lumen from leaking into the bloodstream.

• Integral to tissue polarity:

  • Apical Side: Faces the gut lumen, involved in nutrient transport.

  • Basolateral Side: Faces the bloodstream, also involved in transport.

• Functions:

  • Maintains separate functions and prevents the intermingle of materials in different cell compartments.

Structure of Tight Junctions

• Composed of transmembrane proteins from adjacent cells that adhere tightly across the extracellular matrix.

• They form rows, contributing to a robust barrier against leaking materials.

3. Gap Junctions

• Structure:

  • Comprised of six transmembrane proteins (connexins) forming a pore about 1.4 nanometers wide.

  • Can open and close based on ion concentration and pH levels.

• Functionality:

  • Allow the passage of small ions and molecules (e.g., water, ion, nucleotides).

  • Essential for rapid electrical signaling in tissues, especially in the heart and nervous system.

• Importance in physiology:

  • Provides rapid communication between cells and enables coordinated actions (e.g., heart muscle contractions, nerve impulse propagation).

4. Anchoring Junctions

• Serve to hold cells together under mechanical stress and are critical for tissue integrity.

a. Cell-Cell Anchoring Junctions

• Adherent Junctions:

  • Utilize cadherins to link adjacent cells through their cytoskeletons (actin microfilaments).

  • Involves homophilic interactions requiring calcium ions.

  • Creates a continuous adhesion belt around epithelial cells, enhancing mechanistic strength and cohesion.

• Desmosomes:

  • Provide structural strength by anchoring to intermediate filaments (e.g., keratin).

  • Composed of cadherins (desmogleins and desmocolins).

b. Cell-ECM Anchoring Junctions

• Focal Adhesions:

  • Anchor cells to ECM via integrins connected to the actin cytoskeleton.

  • Involved in cell movement and signaling.

• Hemidesmosomes:

  • Connect intermediate filaments in epithelial cells to the ECM via integrins.

5. Clinical Relevance of Cell Junctions

• Loss of junction function can lead to cancer metastasis, where epithelial cells lose adhesive properties and become migratory.

• Mutations affecting cadherin expression correlate with increased invasiveness in cancer cells.

Summary of Junction Types

• Occluding Junctions (Tight Junctions): Prevent leakage, maintain polarity in epithelial cells.

• Adherent Junctions: Link adjacent cells and enhance mechanical stability.

• Desmosomes: Structure connection between cells through intermediate filaments.

• Focal Adhesions: Integrin-mediated connection of cells to the ECM, crucial for cell signaling and movement.

• Hemidesmosomes: Anchor cells to ECM, particularly in stationary cells.

• Gap Junctions: Facilitate direct communication and signaling between cells via small molecules and ions.

1. Differences Between Junctions:

   • Occluding Junctions (Tight Junctions):

     • Seal gaps between epithelial cells and prevent leakage of substances across epithelial layers.

   • Anchoring Junctions:

     • Hold cells together and stabilize tissue integrity.

     • Include subtypes like cell-cell and cell-ECM anchoring junctions, such as adherens junctions and desmosomes.

   • Channel-Forming Junctions (Gap Junctions):

     • Allow direct passage of small, water-soluble molecules between adjacent cells.

2. Tight Junctions:

   • Formed by transmembrane proteins that seal epithelial cells near their apex.

   • Prevents diffusion of materials between the gut lumen and the bloodstream, maintaining polarity of epithelial cells, where the apical side faces the gut lumen, and the basolateral side faces the bloodstream.

3. Gap Junctions:

   • Comprised of six transmembrane proteins (connexins) forming a pore about 1.4 nanometers wide.

   • These pores can open and close in response to ion concentration and pH levels, allowing the passage of small ions and molecules.

4. Regulation of Solutes in Gap Junctions:

   • The opening and closing of gap junctions are regulated by ion concentrations and pH levels, which determine whether small molecules and ions can pass through.

5. Comparison of Adherens Junctions and Desmosomes:

   • Adherens Junctions:

     • Utilize cadherins that link adjacent cells through their cytoskeletons (actin microfilaments) and require calcium ions for their function.

   • Desmosomes:

     • Provide structural strength by anchoring to intermediate filaments (e.g., keratin) and also use cadherin proteins (desmogleins and desmocolins).

6. Comparison of Focal Adhesions and Hemidesmosomes:

   • Focal Adhesions:

     • Anchor cells to ECM using integrins connected to actin cytoskeleton, play a role in cell movement and signaling.

   • Hemidesmosomes:

     • Connect intermediate filaments in epithelial cells to the ECM via integrins, primarily anchoring the cells.

7. Calcium's Effect on Adherens Junctions:

   • Calcium ions are essential for homophilic interactions between cadherins in adherens junctions, facilitating the adhesion and structural integrity of the junctions.

8. Role of Catenins:

   • Catenins link cadherins to the actin cytoskeleton, playing a vital role in regulating cell adhesion and signaling processes during tissue formation.

9. Assembly of Adherens Junctions:

   • Adherens junctions are assembled through the clustering of cadherins and their linker proteins such as catenins.

   • Rac and Rho are involved in cytoskeletal dynamics and are relevant during the assembly and organization of adherens junctions.

10. Sensing Tension at Adherens Junctions:

    • Cells linked by adherens junctions can sense mechanical tension and respond by altering the cytoskeleton and cell signaling pathways to adapt to mechanical stress.

11. Adhesion Belt and Nervous System Development:

    • An adhesion belt formed by adherens junctions creates a continuous adhesion around epithelial cells, which is crucial for the organization during the development of the vertebrate nervous system.

12. Cell Junctions and Cancer Progression:

    • Loss of junction function can lead to cancer metastasis, as epithelial cells lose their adhesive properties and become migratory. Mutations affecting cadherin expression correlate with increased invasiveness in cancer cells.

-       Dietary oils decrease levels of Claudin and Occludin mRNA in gut cells, material would leak between gut and cells

-       Actin based structure: contractile bundle

-       Adherence junction assembles: Rac

-       deleterious mutation in the GEF regulating Rho GTPase: failure to exchange Rho’s GDP to GTP = failure of contractile bundles along the adhesion belt, natural tube wont close

-       Breast duct cells malignant would show less desmoglein than normal cells