Junctions and Adhesions Flashcards
Types of Cell-Cell
Interactions
Cell-Type Recognition
1) Homotypic
2) Heterotypic
Molecular Interactions
1) Homophilic
2) Heterophilic
Timing
1) Permanent
2) Transient
Homotypic Adhesion – An
experimental example
Developing embryo
Dissociated into single cells
Allowed to re-associate
Cells of a particular type e.g. liver or kidney form aggregates
consisted only of liver and kidney cells
Sponge
If cells of a sponge are
separated, they will eventually
reassemble into a whole
sponge via homotypic
interactions.
Species specific
2 different sponges would
reassemble into 2 separate
sponges.
Membrane glycoproteins
recognise each other
Examples of heterotypic
adhesion
Fertilisation Embryo implantation
Leukocyte extravasation
TJ Proteins
Three types of transmembrane
proteins found in the tight
junction:
Claudins (CLDN)
Occludins (OCLN)
Junctional adhesion
molecule (JAM)
Bind to actin filaments
Maintain cell polarity –
contribute to cell shape, position
and location of proteins in
membrane
Cell Polarity
The spatial difference in
shape, structure and
function
* Different expression
characteristics
* Examples
- Epithelial cell (Diagram)
- Migratory cells
Cell polarity dictates distribution of
proteins
- Confocal microscopy – imaging through cells a thin
slice at a time - Tight junctions regulate this
Tight Junctions form selective barriers
between cells
Paracellular transport – intercellular
movement of substance between cells
Dynamically regulated to control paracellular
solute and ion transport
- Example – reabsorption of Cl- ions in urine
formation
- Example – Glucose absorption in the gut
Fast
Fast:
Through ion
channels
embedded
within
junction
Slow
Slow:
Solutes that can’t
pass, requires
strands to
gradually break
sequentially
Gates and Fences
A gate for ions and other
solutes.
A physical barrier against
water, allergens, pollutants and
bacteria – role in innate
immunity.
A fence to prevent apical and
basolateral transmembrane proteins
from moving into the wrong domain.
Adherens Junction = adherence
Hold epithelial and endothelial cells together.
Links to the actin cytoskeleton.
E-cadherin joins to a range of adaptor proteins
Different types of Adherens Junction
Serve to hold cells together:
* Epithelium
* Synapses
* Cardiac muscle cells
* Between layers of myelin
sheath
Cell adhesion molecules found
within the Adherens Junction
Cell adhesion molecules (CAMS) comprise of two classes:
Those requiring Ca2+ for adhesion – most important
Cadherins
Ca2+ - independent – N-CAMS are neural cell adhesion
molecules
Cadherins
Family of Ca2+ dependent cell-cell adhesion molecules
Cadherins are divided into several classes:
E-cadherins (classical cadherins)
P-cadherins
N-cadherins
R-cadherins
VE-cadherins
All integral membrane proteins (720-750 amino-acids)
Experiment
- Epithelial cells with or
without Calcium - Stain for E-cadherin
- Calcium required for
correct folding and
localization of protein
Calcium-dependent Cadherins Mediate Adhesion between Cells
- Ca2+ ions are
situated between
cadherin molecules - Provide rigidity to
the extracellular
portion of the
protein
β-catenin - A linker
Links Cadherins to actin
* Integral part of cell signalling pathways
* Can also act as a transcription factor
* Mutated in many cancers
Adherens junctions: Catenin interacts with Cadherin
Cell adhesion molecules (CAMS) comprise of two classes:
Those requiring Ca2+ for adhesion – most important
Cadherins
Ca2+
- independent – N-CAMS are neural cell adhesion
molecules
Calcium-independent NCAMs Mediate Adhesion between Neural
Cells
- Do not require
calcium binding to
promote adhesion - Expressed only in
neural cells –
homophilic adhesion - Different splice
variants
Continued
Permits strong adhesion in
adult neurons.
Polysialic acid (PSA) binding
is a post-translational
modification.
Changes shape and function
of NCAMs – less adhesive
Results in a low-affinity
interactions – important for
development
A closer look at Desmosomes
Desmoglein and
Desmocolin
Attach to adaptor
proteins
Weld cells together!
Resist stress so are
abundant in skin and
cardiac muscle
What happens when desmosomes
go wrong?
Patients with damaged or
missing desmosomes
have blistering diseases.
Epithelia become badly
disorganised and sheets
of cells are easily
dislodged.
Tissue engineering
approaches offer
promising treatment
options.
Gap Junctions are composed of
Connexin
Allow direct transfer
of molecules between
adjacent cells
Connexin
Six Connexins form
hydrophilic channel =
Connexon
Connexons make Gap
junctions
Six Connexins
form hydrophilic
channel =
Connexon
More than 20
Connexin family
members
Adjacent cells form
intercellular
channels
Gap Junctions Allow Direct Transfer of Molecules between Adjacent Cells
Molecules up to 1200 Da can pass through.
Proteins and nucleic acids do not pass through
Electrical signals can pass through
Continued
Cluster into ‘plaques’
Can contain 1000s of channels
At least 20 different connexin proteins in humans –
Make a multitude of connexons
Can form homotypic or heterotypic junctions with
neighboring cells
important role in cell-cell communication – electrical
signals, second messenger molecules e.g. cAMP
Cell movement
Cells that participate in defense
against foreign organisms (white
blood cells) must move from blood
to tissues
Free floating unattached cells move
into tissues in a process called
EXTRAVASATION
How do circulating Immune Cells
attach?
Selectins – the biological equivalent
of hand grabbing a paddle
Schematic of white blood
cell in vessel
Selectins expressed by
vascular cells (paddle)
Carrier protein/Sialyl
Lewis (your arm)
* A series of broken
adhesions bring the
leukocyte to a ‘rolling
stop’.
Extravasation
Successive formation and breakage of cell-cell contacts
between white blood cells and endothelial cells lining blood
vessels – discontinuous cell-cell adhesion
Key protein in contact process – P-selectins (blood facing
surface)
Passing white blood cells (WBCs) adhere weakly to the
endothelium but the force of the blood flow means that
WBCs are “slowed” as opposed to being “trapped”
They roll along the surface of the endothelium
