Lecture 23: Cell Junctions and Cell Adhesions Flashcards
How is stress transmitted in epithelial tissue vs connective tissue?
4 Types of cell junctions in animal cells?
Anchoring Junctions
– Include cell-cell and cell-matrix interactions
– Transmit external stress from across the plasma membrane to the underlying cytoskeleton
Occluding Junctions
– Form a permeability barrier between cells in an epithelia sheet
Channel forming Junctions
– Create cytoplasmic continuity between adjacent cells for the passage of small molecules
Signal Relay Junctions
– Allows extracellular signals to be passed from one cell to another
– Some anchoring junctions and channel forming junctions also conduct signaling
adherens junctions and desmosomes are ___
cell-cell anchoring junctions
actin-linked cell matrix junctions and hemidesmosomes are____
cell-matrix anchoring junctions
tight junctions are ___
occluding junctions
Gap junctions are ___
channel forming junctions
tight junction
seals gap between epithelial cells
adherens junction
connects actin filament bundle in one cell with that in the next cell
desmosome
connects intermediate filaments in one cell to those in the next cell
gap junction
allows the passage of small water-soluble molecules from cell to cell
actin-linked cell-matrix junction
anchors actin filaments in cell to extracellular matrix
hemidesmosome
anchors intermediate filaments in a cell to extracellular matrix
_____ link the cytoskeleton to extracellular structures
Transmembrane proteins
Cell-cell interactions are mediated by the ____ family of transmembrane anchors
cadherin
Cell-Matrix interactions are mediated by the ____ family of transmembrane anchors
integrin
Anchoring Junctions function
• Provide mechanical strength
– Especially important to tissues encountering severe mechanical stress like heart, muscle, and skin
• Connect the cytoskeleton to neighboring cells or the extracellular matrix
Anchoring Junctions are composed of what two main classes of proteins?
– Intercellular anchor proteins
– Transmembrane adhesion proteins
Types of Anchor Junctions
– Adherens junctions
– Desmosomes
– Hemidesmosomes
– Focal Adhesions
Cadherins
- Ca2+-dependent cell-cell adhesion
- Present in adherens junctions and desmosomes
- Found in virtually all cells and tissues
Cadherin superfamily
Cadherins mediate ____ adhesion
homophilic
Cadherin structure and function
How do cadherins play a role in development?
Cell with similiar subclasses of cadherins expressed on their surface stick together because of homophilic binding
Cadherins mediate cell-cell adhesion by a homophilic mechanism
• Tissue culture cells (that normally do not express N or E-cadherins) can be made to express either N- or Ecadherin.
• The resulting population self selects based on homophilic interaction of the individual cadherins
Which proteins link cadherins to actin filaments?
- p-120 catenin
- Beta-catenin
- Alpha-catenin
- vinculin
Adherens junctions
- Connect bundles of actin filaments between cells
- Can form adhesion belts (zonula adherens) in epithelial layers
- Transmembrane adhesion proteins belong to the cadherin family
- Intracellular anchoring proteins
– Catenins
– Vinculin
– α-actinin
• Cells must be attached by adherens junctions for tight junctions to form
Adherens junctions structure
Early formation of adherens junctions
Mechanotransduction in an adherens junction
Uses of adherens junctions in development
Desmosomes
- Connect intermediate filaments between cells
- The type of intermediate filament attached is cell type specific
– Keratin filaments in most epithelial cells such as skin
– Desmin filaments in heart muscle
Transmembrane adhesion proteins of desmosomes belong to the cadherin family:
– Desmoglein
– Desmocollin
Intracellular anchoring proteins of desmosomes?
– Plakoglobin (γ-catenin)
– Desmoplakin
– Plakophilin
Desmosome Model
Hemidesmosomes
- “Half desmosomes” that connect intermediate filaments to the basal lamina
- Morphologically similar to desmosomes Transmembrane adhesion proteins belong to the integrin family
– Extracellular domain of the integrin binds to laminin (more later)
• Intracellular anchor protein
– Plectin
Desmosomes and hemidesmosomes link to the ____ network
intermediate filament
____ mediate transient cell-cell adhesions in the bloodstream
Selectins
Selectins
– Cell surface, carbohydrate binding proteins (lectins) – Ca2+-dependent cell-cell adhesion
– L-selectins
• While blood cells
– P-selectins
• Platelets
– E-selectins
• Activated endothelial cells
The structure and function of selectins
Cell Adhesion Molecules (CAMs)
• Cell surface transmembrane proteins
– Cell-cell adhesion
– Cell-matrix adhesion
- Some are Ca2+-dependent, while others are Ca2+- independent
- Initially identified using antibodies to cell surface molecules
- Antibodies to key CAMs were capable of inhibiting cell-cell adhesion in the test tube
Ig superfamily Cell Adhesion Molecules (CAMs) structure
Tight Junctions
- Occluding junctions in vertebrates
- Also known as Zonula occludens (ZO)
- Provide a barrier role in most epithelia
- Prevent protein and lipid diffusion in the plasma membrane allowing for polarization
– Apical vs. basolateral membrane
• Variable permeability barrier between cells
– Cell type dependent, bladder epithelial tight junctions are 104 X less permeable to inorganic ions like Na+ than intestinal epithelia
Tight junction model
What are the tight junction proteins?
claudin and occludin
Claudin and occludin also bind to peripheral membrane proteins called ___ proteins that anchor the sealing strands to the actin cytoskeleton
ZO
ZO proteins form ____ at tight junctions
scaffolds
Septate Junction
Occur in invertebrates like Drosophila Functionally similar to tight junctions Different in structure and appearance
Gap junctions
- Most cells in most tissues are in communication with neighboring cells by gap junctions
- Made up of membrane-spanning channel-forming proteins called connexins
- The channels or connexons have a maximal pore size of ~ 1.5nm
- Allow the passage of small molecules but not proteins
– Inorganic ions, sugars, amino acids, nucleotides, etc
Anatomy of Gap junctions
- Each connexin monomer has four membranespanning segments
- Humans have 14 different connexin genes
- Six monomers assemble into a connexon
- Different connexin subunit assemblies can produce different connexons
- Connexons from adjacent cells interact to form an intercellular channel
Gap junction diagram
Structure of Gap Junction
Gap junctions have diverse functions
• Electrical synapse
– Direct coupling allows the propagation of an action potential from one cell to another without the need for a chemical intermediate (much faster)
• Sharing of metabolites helps coordinate activities
– Glycogen breakdown in response to hormonal stimulation in the liver
– Hepatocytes not directly stimulated by hormone (potentially several cell layers away from a capillary and the source of the hormone) detect a signal by sharing a second messenger through gap junctions
• Communication during development
Connexin turnover
Connexins are added to the edges and removed from the middle
Regulators of gap junction permeability?
– pH
– Cytosolic Ca2+ concentration
– Extracellular signals
• Some neurotransmitters like dopamine
Why regulate gap junction permeability?
– Cells need a way to close down these connection to prevent widespread damage when one participant is damaged
Plasmadesmota
“Plant Gap Junctions” Since plants have a rigid cell wall, a specialized structure is required to bridge it
