Lecture 1: recap on epithelial and connective tissues
Epithelia and connective tissue are main components of tissues and organs
Difference epithelia and connective tissue:
- Skin has dead cells and is harder while gut is for more protection
Cell-cell connection and Cell-ECM connection:
- Keratine filaments = in green
Cell-cell (1-3) and cell-matrix (4-5) adhesions in (epithelial) cells
Occluding = separation
Anchoring = attachment
,Cell-cell adhesion
Tight junctions are occluding junctions (zonula occludens, ZO)
- Tight junction are linked to (contractile)actin cytoskeleton via adaptors (including ZO-1,2,3)
- Transmembrane CAMs: claudins, occludins and JAMs
- Cytoskeleton: actin filaments
- TJ are majorly assembled by claudins and occludins with each two extracellular loops
➔ Form homophilic interactions on the other membrane side
➔ Form networks of paired intramembrane strands (‘kissing points’)
- Run perpendicular to direction of paracellular space and direction of ion transport
- Main functions:
o Seal gaps between epithelial cells
o Selective paracellular transport
o Role in maintaining apical/basolateral cell polarity
Adherens junctions and desmosomes: anchoring cell-cell adhesion complexes:
Model for the generation of cell-cell adhesion
- Cam cis interactions – intracellular lateral interaction
o Forms lateral clusters within the plasma membrane
- Trans interactions – intracellular adhesive interactions
o Generate strong, Velcro- like adhesion between the cells
- Trans and cis interactions are mutually reinforcing
The strand swab mechanism for trans interactions of classical cadherins
- Requires Ca2+ for homophilic interactions
, - Clustered by trans interactions at adherens junctions on adjacent cells (‘strand swab’
mechanisms)
Cadherins form adherens junctions in cooperation with the actin cytoskeleton
- Adherens junctions assembly favors α-catenin dimerization
→ Force transmission and stressfiber formation
➔ Mature adherens junctions confer shape and mechanical strength to cells and tissues
Desmosomal cadherins form desmosomes in cooperation with intermediate filaments
, Molecular organization of adherens junctions and desmosomes
Summary:
Adherens junctions and desmosomes:
- Structure
o Transmembrane CAMs: cadherins (Ca2+ dependent, cis and trans
interactions)
o Desmosomal cadherins have longer cytoplasmic tails than ‘classical’
cadherins → CAM cytoplasmic domains associate with different adapter
proteins that link them to the cytoskeleton / signaling pathways
o Contain various types of cadherins, adaptor proteins, cytoskeleton
- Main function
o Adherens junctions
▪ Initiation and stabilization of cell-cell adhesion
▪ Confer shape and mechanical strength on cells and tissues
▪ Organization of cell structure by being linked to cytoskeleton
dynamics/signaling pathways
o Desmosomes
▪ Cell shape
▪ Strength and rigidity of epithelia
Gap junctions are channel-forming cell-cell junctions
Molecular structure and organization of connexins in gap junctions
- Channel consists of 2 connexons with each 6 connexins
- Extracellular loops form tight seal
- C-terminal end interacts with cytoplasmic proteins
- Channel around 8 nm size in diameter
Epithelia and connective tissue are main components of tissues and organs
Difference epithelia and connective tissue:
- Skin has dead cells and is harder while gut is for more protection
Cell-cell connection and Cell-ECM connection:
- Keratine filaments = in green
Cell-cell (1-3) and cell-matrix (4-5) adhesions in (epithelial) cells
Occluding = separation
Anchoring = attachment
,Cell-cell adhesion
Tight junctions are occluding junctions (zonula occludens, ZO)
- Tight junction are linked to (contractile)actin cytoskeleton via adaptors (including ZO-1,2,3)
- Transmembrane CAMs: claudins, occludins and JAMs
- Cytoskeleton: actin filaments
- TJ are majorly assembled by claudins and occludins with each two extracellular loops
➔ Form homophilic interactions on the other membrane side
➔ Form networks of paired intramembrane strands (‘kissing points’)
- Run perpendicular to direction of paracellular space and direction of ion transport
- Main functions:
o Seal gaps between epithelial cells
o Selective paracellular transport
o Role in maintaining apical/basolateral cell polarity
Adherens junctions and desmosomes: anchoring cell-cell adhesion complexes:
Model for the generation of cell-cell adhesion
- Cam cis interactions – intracellular lateral interaction
o Forms lateral clusters within the plasma membrane
- Trans interactions – intracellular adhesive interactions
o Generate strong, Velcro- like adhesion between the cells
- Trans and cis interactions are mutually reinforcing
The strand swab mechanism for trans interactions of classical cadherins
- Requires Ca2+ for homophilic interactions
, - Clustered by trans interactions at adherens junctions on adjacent cells (‘strand swab’
mechanisms)
Cadherins form adherens junctions in cooperation with the actin cytoskeleton
- Adherens junctions assembly favors α-catenin dimerization
→ Force transmission and stressfiber formation
➔ Mature adherens junctions confer shape and mechanical strength to cells and tissues
Desmosomal cadherins form desmosomes in cooperation with intermediate filaments
, Molecular organization of adherens junctions and desmosomes
Summary:
Adherens junctions and desmosomes:
- Structure
o Transmembrane CAMs: cadherins (Ca2+ dependent, cis and trans
interactions)
o Desmosomal cadherins have longer cytoplasmic tails than ‘classical’
cadherins → CAM cytoplasmic domains associate with different adapter
proteins that link them to the cytoskeleton / signaling pathways
o Contain various types of cadherins, adaptor proteins, cytoskeleton
- Main function
o Adherens junctions
▪ Initiation and stabilization of cell-cell adhesion
▪ Confer shape and mechanical strength on cells and tissues
▪ Organization of cell structure by being linked to cytoskeleton
dynamics/signaling pathways
o Desmosomes
▪ Cell shape
▪ Strength and rigidity of epithelia
Gap junctions are channel-forming cell-cell junctions
Molecular structure and organization of connexins in gap junctions
- Channel consists of 2 connexons with each 6 connexins
- Extracellular loops form tight seal
- C-terminal end interacts with cytoplasmic proteins
- Channel around 8 nm size in diameter
