ANHB3323 (9) - cell-cell interactions

2 Main ways animal cells are bound together

Epithelial cells:

• Anchored cell to cell and cell to ECM

Mesenchymal cells (Cancer Type):

• cell-ECM dominant

Cell Junction types

1. tight junction

2. cell-cell anchoring junctions

3. channel-forming junctions

4. cell-matrix anchoring junctions

Tight junctions

seals gap between epithelial cells - prevent uncontrolled molecule movement

• contain strands of transmembrane adhesion proteins

Proteins:

• Claudin and Occludin

Mice with no claudin-1 gene

• fail to make tight junctions = lose water rapidly

Gap Junctions - channel forming

Allows passage of small water-soluble molecules from cell to cell

• connect cells electrically (ions) and metabolically (molecules)

• Diameter of gap dictates size of molecules that can pass

Gap junction structure

Connexins

• 2 types of proteins that make up the channel

Connexon

• Half og channel

• Heteromeric (mix of the two types of connexins)

• Homomeric (only one type of connexin)

Intercellular channel

• both sides of the channel from each cell combines

Cell-cell anchoring junction types

Adherens junction (actin filament)

Desmosomes (intermediate filaments)

Adherens junction

connects actin filament bundle in one cell with that in the next cell

Adherens junction mechanism

Tension (extracellular) is required to expose the binding side of the actin fimalent and unfold the alpha-catenin molecule

• allows for binding of vinculin

• Junction is activated by tug of war tension between cadherins

Desmosomes

connects the intermediate filaments in one cell with that in the next cell

• utilise non-classic cadherin proteins

• Connected to hemidesmosomes via intermediate filament

Desmosome elements and their protein types

Cytoskeleton→ Intermediate filament

Intracellular adaptor protein

• plakoglobin, plakophilin, desmoplakin

Transmembrane Adhesion protein

• desmoglein, desmocollin (non-classical cadherin proteins)

Extracellular Ligand

• desmoglein, desmocollin

Cell-matrix anchoring junctions (types)

Actin linked cell-matrix junction

Hemidesmosome

Actin-linked cell matrix junction

Anchors actin filaments in cell to extracellular matrix

Adhesion proteins:

• Integrin heterodimer (with alpha (24) and beta (8) subunits)

Adaptor proteins:

• Talin & Vinculin

Hemidesmosome

Anchors intermediate filaments in a cell to extracellular matrix

adhesion proteins

• Integrin a6B4 + Collagen XVII

adaptor proteins

• BP230 + Plectin

Transmembrane adhesion proteins

Go through the cell membrane to adhere to something outside

• connects to intracellular adaptor proteins → which link to the filaments

(found in anchoring junctions, cell-cell or cell-ecm)

Intracellular adaptor proteins

Connect the cytoskeleton filaments to the transmembrane adhesion membrane.

cell-cell vs cell-ecm transmembrane adhesion proteins

Cell-cell = connect same kind of adhesion proteins

Cell-ECM = asymmetric

Classical Cadherins - adhesion molecules

A transmembrane membrane adhesion protein

• The extracellular part has 5 domains, separated by flexible hinge regions

• Each hinge has calcium channels that create a velcro-like mechanism holding cells together

Present homophilic bonding which allows for sorting by types and level of expression

What do Cadherins use to connect to cytoskeleton?

Catenins and Vinculin used to connect to actin filament

• happens via force feeling upon homophilic binding

Activation of integrin leads to...

intracellular signalling

(integrin beta subunit will be activated upon binding to ECM = recruits intracellular adaptor proteins)