Cell junctions, cell adhesions, and the ECM Flashcards
Of all the interactions between cells in a multicellular organism, the most fundamental are
those that hold cells
together
Cells cling to one another through _______ junctions, or through the _______
Cell-cell, ECM
Attachments to other cells and to the ECM control the
___________ of each cell’s internal structure.
orientation
Two basic building strategies:
1) The strength of the ECM, and
2) The strength of the cytoskeleton within the cell and cell-cell adhesions that tie the cytoskeletons of
neighboring cells together.
What underlies many diseases (With ECM)
Defects in the apparatus of cell junctions, cell adhesion and ECM underlie many diseases
Most animal tiessues fall into one or other of two broad categories:
1) connective tissues
2) epithelial tissues
Connective tissues
Such as bone and tendon have abundant ECM and cells are sparse within it. The matrix is rich in fibrous polymers such as collagen and it is the matrix rather than cells that bear mechanical stress.
Epithelial tissues
Such as the lining of the gut or skin, cells are closely bound together into sheets called epithelia. The ECM is scarce, consisting mainly of a thin basal lamina. Cells are linked via cell-cell adhesion and stress is dispersed this way
4 main functions of junctions
- Anchoring junctions
- Occluding junctions
- Channel-forming junctions
- Signal-relaying junctions
Anchoring junctions
includes both cell-cell adhesions and cell-matrix adhesions, transmit stresses and are tethered to cytoskeletal filaments inside the cell
Channel-forming junctions
create passageways linking the cytoplasm of adjacent cells
Occluding junctions
seal the gap between cells in epithelia so as to make the cell sheet into an impermeable (or
selectively permeable) barrier
Signal-relaying junctions
allow signals to be relayed from cell to cell across their plasma membranes at sites of cell-cell
contact.
2 types of attachment sites for anchoring junctions
- actin filament attachment sites
- intermediate filament attachment sites
Actin filament attachment sites
- cell-cell junctions (adherens junctions)
2.cell-cell matrix junctions (actin-linked-cell-matrix adhesions)
Intermediate filament attachment sites
- cell-cell junctions (desosomes)
- cell-matrix junctions (hemidesosomes)
types of occluding junctions
- tight junctions (in vertebrates)
- septate junctions (in invertebrates)
types of channel-forming junctions
- gap junctions (animals)
- plasmodesmata (plants)
types of signal-relaying junctions
- chemical synapses (nervous system)
- immunological synapses (immune system)
- transmembrane ligand-receptor- cell-cell signalling (Delta-Notch, ephrin-Eph, etc).
hemidesosome vs desosome
if one on each cell connect to eachother there are 2, but if connecting to basal lamina there would only be one hence the “hemi”
cadherin mediates which junction
adherens junctions - links actin cytoskeleton between 2 cells
Linking the cytoskeleton to the ECM is always done at the _______side of an epithelial cell, actin through the ________signaling and IF through the _____________
basal, integrin, hemidesosomes
At each of the 4 types of anchoring junctions, the central role is played by
transmembrane adhesion proteins
Transmembrane adhesion proteins
span the membrane, one end linking the cytoskeleton inside the cell and the other end linking to other structures outside it
The ________ superfamily
mediates attachment of cell
to cell
cadherin
The _______ superfamily
mediates attachment of cell
to matrix
integrin
What mediates attachments of cell to cell
cadherin superfamily
What mediates attachments of cell to matrix
integrin superfamily
Anchoring junctions: cell-cell
- Adherens junctions - cadherin - actin filaments
- Desosomes - desosome - IF
Anchoring junctions: cell-matrix
- Actin-linked-cell-matrix adhesion - integrin- actin filaments
- Hemidesosome - hemidesosome - IF
Cadherins mediate ______ dependent cell-cell adhesion in all animals
Ca2+
True or false: cadherins are present in all multi and unicellular animals
False: only multicellular
Removing Ca2+ from extracellular medium causes
adhesions mediated by cadherins to come apart: (fall apart)
The first 3 cadherins that were discovered were named according to the main tissues in which they were found:
- E-cadherin on epithelial cells
- N-cadherin on nerve cells
- P-cadherin on cells of the placenta.
Is E-cadherin the only cadherin found on an epithelial cell?
No, N cadherin can be on an epithelail cell, but in lower abundance
Cadherins mediate _______ adhesion
homophilic
Calcium present at greater than imM
promotes rigid structure by binding to hinge regions
Calcium drops below 1mM
lose binding, cadherin folds in on itself and cant interact with neighbouring cell
Velcro principle and what is the benefit
instead of having one really strong interaction, we
have multiple interactions that are lower in affinity. Benefit- this cell, which could be ina blood vessel, may get injured or may need to migrate, it needs to be able to make and break thses connections readily.
Unlike receptors for soluble signal molecules, which bind their specific ligand with high affinity, cadherins typically bind to their partners with relatively
low affinity
Cadherins mediate highly
selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells
Many cadherin molecules packed side by side collaborate to form an
anchoring junction
What if we have a group of cells
that express high levels of e cadherin and the other group of cells has only a little bit of E cadherin?
most cells express a few different cadherins but will have a “dominant” one that is expressed. What will happen is that the tightest connections will form when there is the most amount of cadherin - cells with less E-cadherin form ring around the center “ball” (cadherins with tightest bonds)
What if you want tissues to be completely seperate and not ahere or communicate at all?
this about mesoderm – giving rise to muscle and ectoderm giving
rise to skin and the nervous system, you cannot have tissues of the skin completely
disconnected from the muscle, they need to be able to interact. They achieve this by
expressing different levels of specific cadherins.
Neural crest gives rise to
The peripheral nervous system
What do cells that become neural crest cells need to do (neural tube)
Migrate out of neural tube, proliferation, migrate and differentiate
What happens to ectoderm when it has high expression of E-cadherin
Infolding of ectoderm, eventually develops into neural tube
What happens when ectoderm inward folds and turns into neural tube
Change towards higher expression of N-cadherin (down-regulate E-cadherin)
What happens at junction of the fold (inward fold of ectoderm, turns into neural tube)
Upregulation of cadherin 6B, inward invagination fuses (like binds like), neural tube closes but be seperate from cells above (ectoderm)
What happens after inward invagination fuses
Seperate population of cadherin 6B can migrate out, differentiate, changes cadherin expression to high levels of cadherin 7, forms neural crest cells and peripheral NS
Adhesion belt composition
A big cluster of cadherins, each one linking to an actin filament and linking these actin filaments to neighbouring cells actin filaments
Adhesion belt role
A bridge of actin across all the epothelial layer that helps give it strength and move in unison
The adhesion belt is very important for forming anything that has an
epithelial sheath (like the ones lining a blood vessel)
Formation of epithelial tube
Start with sheet of epithelial cells, invagination of epithelial sheet caused by an organized tightening of adhesion belt in selected regions of cell sheet, epithelial tube pinches off from overlying sheet of cells, epithelial tube
Cell-cell junctions send signals into the
cell interior
Making and breaking of attachments are important events in
differentiation, proliferation, migration
True or false: WNT would activate genes involved with cadherins (including the cadherins itself)
True
_______ junctions give epothelia mechanical strength
desosome
Desosome junctions give epithelia
mechanical strength
Desosome junctions are structurally similar to adherens junctions but
Link to intermediate filaments instead of actin
Particular type of IF attached to desosome in epthelial vs heart muscle cells
-Keratin filaments in most epithelial cells
-Desmin filaments in heart muscle cells
Difference between desosomes/hemidesosomes compared to adherens junctions structure
IF junctions do not create a belt b/c they are not polar, they are rope like structures that can go in multiple directions across cell
