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Lecture

Lecture 3

10 Pages
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Department
Biology
Course Code
BIO120H1
Professor
Jennifer Harris

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Tuesday, March 3, 2009
- This week we’re going to be discussing cell junctions & adhesion b/w
cells.
- They connect cells together or they connect cells to the matrix that
underlies cells.
Mechanically attach cells to cells or the extracellular matrix
Seal the contacts b/w the cells
Allow chemical or electrical signals to pass from cell to cell (through
these channels)
- Today well focus on anchoring junctions.
- Anchoring junctions hold cells together mechanically it attaches them
to one another or to the matrix.
- On this diagram, hes drawn to scale a typical size of a mammalian cell,
~50 microns wide & the tiny little dot/speck is a 50 nm long cell adhesion
molecule. How can these individual molecules deal with these relatively
massive cells?
- We heard about this a little bit when we talked about the actin
cytoskeleton & how actin molecules, which are also very small, similar to
the size in the diagram, we saw that they could impact cell structure by
assembling huge networks inside the cell & pushing against the plasma
membrane, pushing the plasma membrane outwards to change cell shape.
Here that same principle applies.
- These cell adhesion molecules, these tiny cell adhesion molecules,
assemble larger complexes & these complexes have 2 features that
overcome this challenge of size (as listed in the slide).
- Diagram: Here is one single cell & here is a cell-cell adhesion complex
these would be a large number of cell adhesion molecules clustered
together in that complex & they connect to the cytoskeletal networks.
- So you can follow protein-protein interactions b/w the cell adhesion
complex through the cytoskeleton to another cell adhesion complex
through the cytoskeleton of that cell, through another cell adhesion
complex & so on so you have a huge assembly of proteins within these
cells supporting the tissue support.
- How can clustering cell adhesion molecules increase the strength of
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their binding?
The binding strength b/w 2 molecules via a single binding site
The total binding strength b/w 2 molecules or complexes involving
multiple binding sites
- So you might think that this total binding strength here in the avidity
would be just all of those individual interaction affinities added together
to create the overall binding strength. So if there were say 5 interactions
here & you knew the affinity of each individual one, you could add those
5 together & that would give the total. This is not the case.
The binding strength b/w 2 molecules via a single binding site
The total binding strength b/w 2 molecules or complexes involving
multiple binding sites
- You might imagine that there would be one interaction interface, if this
was sitting on its own, it might have a tendency to break apart at a certain
frequency so it may have the tendency to break apart but if a
neighbouring interaction is still holding on at a different site, thats going
to hold that first one in place & its going to reduce its tendency to break
apart so this is this co-operativity.
- If you have 5 interaction sites all beside one another, if one is about to
break but the other 4 aren’t about to break those 4 sites will keep that first
one in place & keep it bound. So that is why this avidity is higher than the
sum of the individual interaction affinities so you get this real boast of
binding strength b/w the molecules.
- Another feature of this is that the pulling forces are distributed among
many proteins & this is significant if you think about 2 cells that might be
trying to crawl away from one another, or move away from one another
or being pushed by physical stress to separate from one another but these
many molecules will hold those cells together.
- This is where you can see the analogy of a Velcro type of effect where
youd have these tiny little loops, right here would be one single cell
adhesion molecule, one thread over here would be the other single cell
adhesion molecule so if those 2 interacting with one another, they’re not
going to be very strong at all but then when we have them all clustered
together into this large cluster here, those 2 Velcro patches will adhere to
one another very strongly.
- So that is one key aspect of cell adhesion complexes is this clustering of
receptors. The other aspect is the linkage to the cytoskeleton inside the
cell.
Adherens junctions (cell-cell)
Focal adhesions (cell-matrix)
Desmosomes (cell-cell)
Hemidesmosomes (cell-matrix)
- There are linkage sites for actin & microtubules. So actin &
microtubules can interact with adherens junctions which are cell-cell
adhesion complexes & also with focal adhesions which are cell-matrix
adhesion complexes.
- Then intermediate filaments, they can attach to specific cell adhesion
complexes the desmosomes that mediate cell-cell & hemidesmosomes
which mediate cell-matrix interactions.
- These are the basic properties of any adhesion complex that are going to
be clustered together & they’re going to be attached to the cytoskeleton
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on the other side of the plasma membrane of the cell & this allows those
adhesion complexes to adhere cells together into a larger tissue.
- Now hes going to talk more specificity about adherens junctions.
- These epithelia are sheets of cells that line our body compartments so
its the most common architecture in our body, it lines all of our organs, it
forms our skin.
- Diagram: can see 2 epithelial cells what you can think of here is these
individual cells are sort of like bricks in a wall, they add up together to
form this sheet of cells & this separates one body compartment from the
other. Here, for example, would be one body compartment, say the lumen
of the gut & on the other side of this would be the underlying tissue. The
adherens junctions are forming right b/w these cells this cell is cutting
cross-section so this adherens junction is actually forming a ring right
around this cell & connecting that cell to all of its neighbours so you can
think of these adherens junctions as acting as mortar in b/w the bricks so
they’re found all around the cells, connecting all the cells together in the
tissue.
Clustered cadherin adhesion receptors
Actin cytoskeleton
- If we look close up at the molecular structure of these adherens
junctions we can see these 2 basic properties of a cell adhesion complex
as listed in the slide.
- Diagram: So we can see that right over here in this diagram so this is
one cadherin receptor in green so it has 5 blobs, a transmembrane domain
in the cytoplasmic tail so you can see this one cadherin forms a dimer
with another one which interacts with another dimer from the other cell &
another one & another one. This is just in 2 dimensions here but this will
form a 3D plaque of all of these receptors interacting with one another in
a cluster. Then these adhesion receptors then run through the plasma
membrane, on the other side they interact with adaptor proteins here in
blue & these adaptor proteins link the adhesion complex to actin
cytoskeleton shown by these red filaments in the diagram.
Five extracellular domains
A transmembrane domain
A cytoplasmic tail
- Here is the structure of the cadherin receptor in more detail, at the
molecular level.
- So for an adhesion molecule or adhesion receptor to mediate adhesion
b/w one cell & another, that receptor has to reach out from one cell &
make contact to another cell in the extracellular space. So these
molecules, they have to be a transmembrane proteins, they have to cross
the plasma membrane so they can reach out into the extracellular space &
contact other cells.
- Diagram: Here in the cadherin structure, there are 5 of these
extracellular domains so here again is one individual cadherin receptor,
this is a 2nd receptor so this is a dimer of the 2. So if we look in the
extracellular space here, we can see 5 of these repeats & each of these
repeats has a specific folded structure of the amino acid residues. So this
would be the N terminus of the protein, this folds into a specific structure
making up that domain & then the C terminus of this then connects to the
N terminus of the next one & this is all one continuous polypeptide all the
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Description
Tuesday, March 3, 2009 - This week were going to be discussing cell junctions & adhesion bw cells. - They connect cells together or they connect cells to the matrix that underlies cells. Mechanically attach cells to cells or the extracellular matrix Seal the contacts bw the cells Allow chemical or electrical signals to pass from cell to cell (through these channels) - Today well focus on anchoring junctions. - Anchoring junctions hold cells together mechanically it attaches them to one another or to the matrix. - On this diagram, hes drawn to scale a typical size of a mammalian cell, ~50 microns wide & the tiny little dotspeck is a 50 nm long cell adhesion molecule. How can these individual molecules deal with these relatively massive cells? - We heard about this a little bit when we talked about the actin cytoskeleton & how actin molecules, which are also very small, similar to the size in the diagram, we saw that they could impact cell structure by assembling huge networks inside the cell & pushing against the plasma membrane, pushing the plasma membrane outwards to change cell shape. Here that same principle applies. - These cell adhesion molecules, these tiny cell adhesion molecules, assemble larger complexes & these complexes have 2 features that overcome this challenge of size (as listed in the slide). - Diagram: Here is one single cell & here is a cell-cell adhesion complex these would be a large number of cell adhesion molecules clustered together in that complex & they connect to the cytoskeletal networks. - So you can follow protein-protein interactions bw the cell adhesion complex through the cytoskeleton to another cell adhesion complex through the cytoskeleton of that cell, through another cell adhesion complex & so on so you have a huge assembly of proteins within these cells supporting the tissue support. - How can clustering cell adhesion molecules increase the strength of www.notesolution.com
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