M8L1 - Cell Adhesion Molecules

H.V. Wilson Sponge Experiment 

• First demonstrated the ability of cells to recognize and adhere to one another 

• Used the cells of 2 sponge species 

• Their indiv cells were seperated using a fine mesh 

• The cells were then mixed together 

• Overtime, the cells from the same species were able to recognize and associate back together 

  • Cells from diff species didn’t associate 

Johannes Holtfreter: Frog Embryo Experiment

• Showed cell recognition and adhesion using frog embryos

• Took cells from 2 different developmental germ layers and seperated indiv cells 

• Similar tissue recognized eachother and associated

• The associations mimicked original embryo organization

What are the three developmental germ layers of an early embryo

1. Endoderm 

2. Ectoderm

3. Mesoderm 

During embryogenesis, how do cells recognize and stay together?

• Requires transmembrane proteins called CAMs (cell adhesion molecules)

• After aggregation, they form specialized junctions stabilizing the cell interactions

• Facilitated communication between adjacent cells 

How are epithelial cells organized, and what do they form in the body?

• Epithelial cells connect along their lateral surfaces to form epithelial sheets.

• These sheets line body cavities and cover surfaces like the digestive tract and skin.

• Each epithelial cell has distinct surfaces:

  • Apical surface: faces the lumen or outside (e.g., with microvilli in the intestine).

  • Basal surface: faces inward and is attached to the basal lamina / basement membrane.

What connects epithelial cells to the underlying extracellular matrix?

• The basal surface anchors to the basal lamina (basement membrane).

• Hemidesmosomes are adhesion complexes that connect the cell’s basal side to the extracellular matrix (ECM), providing structural support.

Which types of adhesion complexes connect the lateral surfaces of epithelial cells?

1. Tight junctions

2. Adherens junctions

3. Desmosomes

4. Gap junctions

Tight Junctions

• zonula occludens 

• Connect adjacent cells below the apical surface 

• It completely seals the space between the cells 

  • Prevents fluid from moving across the layer

  • Restricts diffusion of small molecules in gastrointestinal track to prevent enzyme leakage 

• Done by linear arrays of occludin and claudin 

  • ‘Pinches’ cells together 

Gap Junction Function

• Link the cytosol of one cell to the other

• Allows for integration of metabolic activities of all cells in a tissue by allowing ion/small molecule exchange 

  • Ex. cAMP and Ca++

Diameter of Gap Junction Channels

• 1.5-2 nm

• Allows for free diffusion of molecules up to 1 kDa in size

Gap Junction Structure

• 6 connexin proteins make a hexagonal connexon hemichannel

• One hemichannel will sit in the cell membrane of each connected cell

• Two lined-up hemichannels form a gap junction

• These hemichannels are found in groups to form gap junction rich regions

Gap Junction Applications

• Allows for diffusion convenient for interconnected cells

• They allow for rapid coordination of cardiac muscle contraction 

• They allow for rapid uterine muscle contraction 

• Stimulation of one cell leads to a response shared by many cells through diffusion of secondary messangers 

Gap Junctions in Plant Cells: Plasmodesmata

• Important to the structure and function of phloem 

• Phloem is a system of tubes formed by cells connecting linearly 

• It carries nutrients to the rest of the plant

• Sieve-tube elements are connected by plasmodesmata that form the seive tube plate 

  • They’re metabolically inactive 

  • Companion cells provide ATP and substances to these cells 

  • They’re also ocnnected by plasmodesmata 

• Plasmodesmata also helps with communication through informational molecules

  • Gene transcripts, small RNA, etc.

  • Pathogens also exploit this though

Anchoring Junctions

• Includes:

  • Adherens junctions

  • desmosomes: Link 2 cells together

  • hemidesmosomes: Attach cells to extracellular matrix

• Distinguished by their association with actin filaments

• Through the connections, adherens junctions indirectly connect the actin cytoskeleton between neighbouring cells

Four Families of Cell Adhesion Molecules that Make up Adherens Junctions

1. Cadherins

2. Ig-superfamily

3. Integrins

4. Selectins

Which cell adhesion families form homophilic interactions?

• This means association of similar cells 

• Cadherins 

• Ig-superfamily CAMs

Which cell adhesion families form heterophilic interactions?

• This binds non-similar cells

• Integrins 

• Selectins 

Cadherins Function

• Cell adhesion molecules of adherens junctions

• They’re calcium dependent CAMs mediating homophilic interactions

• They mediate epithelial cell adhesion near the apical surface

What are the three major classes of cadherins

1. E-cadherin (epithelial)

2. N-cadherin (neural)

3. P cadherin (placental)

Cadherins Mechanism

• Adhesion involves

  • transmembrane cadherins

  • cytosolic cofactors 

  • catenins (anchors cadherin to actin)

• Cells do not aggregate into sheets under standard cell conditions

  • E-cadherin must be expressed

  • It’s calcium-dependent

  • Without calcium, E-cadherin cannot function, and cells remain separate.