Cell Adhesion and Signalling Quiz

Cell Adhesion and Cell Signalling

• Multicellular organisms depend on cell adhesion to each other and the extracellular matrix (ECM) for tissue formation.
• Some adhesive interactions are stable, such as the firm adhesion of muscle cells to each other and connective tissues in tendons. Other adhesive interactions are transient, such as leukocytes binding to endothelial cells to prepare for extravasation into tissues.

Cellular Adhesion

• Some examples of stable cell-cell adhesive interactions involve muscle cells connecting to each other and connective tissues for transmitting force from skeletal muscles.

• Examples of transient cell-cell adhesive interactions are those involving leukocytes binding to endothelial cells lining blood vessels as a preparation for extravasation into surrounding tissue. Cells also attach to ECM during cell migration.

Cell Junctions

• Cell junctions include anchoring junctions, occluding junctions, channel-forming junctions, and signal-relaying junctions.

• Anchoring junctions (e.g., adherens junctions and desmosomes) connect actin-linked or hemidesmosomes to the cytoskeleton and help transmit physical forces.

• Occluding junctions (tight junctions) seal gaps between epithelial cells to provide impermeability or selective permeability.

• Channel-forming junctions (gap junctions) allow passage of small molecules and ions between cell cytoplasms, such as neurons or immune synapses.

• Signal-relaying junctions allow signal transduction between cells through cell-cell contact sites such as synapses.

• Cell-cell junctions include those containing classical cadherins (eg E-cadherin), as well as nonclassical cadherins (eg desmoglein) or Ig-like family members (eg NCAM).

Cadherins

• Cadherins are a family of adhesion proteins that mediate calcium-dependent homophilic adhesion.

• Cadherin adhesions individually have low affinity but in combination, they provide strong attachment.

• Different types of cadherins exist, including classical, fat-like, seven-pass transmembrane, protein kinase, desmosomal, cadherin 23 and protocadherins.

Cell Segregation during Embryonic Development

• Cell segregation during embryonic development is an example of cells expressing different cadherins.
• For example, cells expressing E-cadherin differentiate to form the neural tube, whilst cells expressing N-cadherin differentiate to form neural crest cells.

Catenins

• Catenins link classical cadherins to the actin cytoskeleton.
• Extracellular domains of cadherins link together to mediate adhesion
• Cytoplasmic domains are required for linking to the actin cytoskeleton, indirectly via anchor proteins, including catenins (β-catenin also functions in signaling, such as the Wnt pathway)

Gap Junctions

• Gap junctions allow passage of small molecules (ions and molecules like sugars, amino acids, nucleotides and vitamins). and intracellular signaling molecules such as cyclic AMP and inositol trisphosphate between cells.
• Two types of gap junctions exist: Large and small.

Small Molecule Transfer

• Gap junctions allow transfer of small molecules, including inorganic ions, sugars, amino acids, nucleotides, vitamins, cyclic AMP and inositol trisphosphate, between cells.

Tight Junctions

• Tight junctions seal epithelial cells together, preventing the passage of materials between them.
• The sealing strands of occludin and claudin proteins form a tight junction.

Selectins

• Selectins mediate transient, weak interactions.
• Selectins are cell surface carbohydrate-binding proteins that bind to mucins (addressins) on cell surfaces.
• These interactions help move cells through blood vessels.
• Selectins are expressed on white blood cells, platelets and endothelial cells (L, E, and P selectins)

Cell Adhesion Molecules and T Cell Recruitment to Lymph Nodes

• Lymphocytes bind to vascular endothelium (in lymph nodes) via the interaction between L-selectin and vascular addressins.

Cell Adhesion Molecules and Neutrophil Recruitment

• Selectin-mediated adhesion is weak, allowing neutrophils to roll along vascular endothelial cells.

• Interactions between selectins and carbohydrate ligands on neutrophils allow their temporary attachment to blood vessel walls.

• These transient interactions slow down cell movement along the blood vessel wall.

Selectins Regulation

• Selectins are regulated by inflammatory mediators (e.g., TNFα, CXCL8, leukotriene LTB4, histamine, thrombin.)
• These inflammatory mediators can upregulate the expression of selectins, increase cell surface expression of selectins on platelets, and promote platelet aggregation.

Syndecans

• Syndecans are cell surface proteoglycans that mediate cell adhesion to the extracellular matrix (ECM).
• They bind growth factors like FGF, cytokines and other growth factors.

Desmosomes

• Desmosomes are cell-cell adhesion structures found in tissues subjected to mechanical stress.
• They are composed of cadherin-like proteins.
• Desmosomes connect intermediate filaments of the cytoskeleton between the cells.

Integrins

• Integrins mediate cell-matrix and cell-cell adhesion.
• Integrins are non-covalently bound heterodimers.
• Integrins mediate adhesion of cells to the extracellular matrix.
• Integrins physically link intracellular cytoskeletons to the extracellular matrix to attach epithelial cells to basal lamina.

Integrin Activation

• Integrin activation can be either inside-out or outside-in signalling, depending on whether the signal is from inside or outside the cell.
• Inside-out signalling involves intracellular signalling pathways.
• Outside-in signalling involves ligand binding at the extracellular receptor site.

Integrin based cell-matrix adhesion in motile cells

• Focal adhesions and podosomes are examples of integrin-based cell-matrix adhesions involved in motile cells.
• Focal adhesions are found in many cell types.
• Podosomes are restricted to specialized cells.
• These features are important for cell spreading, motility and matrix remodelling.

Integrins in Cell-Cell Adhesion

• Integrins can bind other cellular adhesion molecules.
• This is seen in T cell binding to ICAM molecules on antigen presenting cells.