18 – cells in their environment I: Adhesion & the Matrix Flashcards

1
Q

Cells interactions

A

Cells interact & receive signals from their environment:

-Physical connections
–How cells build & regulate

-Chemicals signals

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2
Q

2 types of Cell adhesion (physical interactions) & the cells involved

A

Cells stick to each other & to their surroundings

Cell-cell adhesions
-CAM – cell adhesion molecule

Cell-matrix adhesions
-Adhesion receptors & CAMs

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3
Q

Cells care about.. & want to

A

who they stick to

and want to stick to different partners

cells are expressing all of these different types of cell adhesion molecules tells us that cells must want to be able to stick to different types of partners and that they’ll express a particular type of cell adhesion molecule in order to enable them to stick to one type of neighbor and not then to another.

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4
Q

Cell-matrix adhesions

A

Cell adhesion molecules - CAM

Cells express wide/diverse range of CAMs

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5
Q

Cell-Cell adhesion, molecule involved

A

-Cadherins: E-cadherins

sticking out into the extracellular space as a series of globular domains.

touching one another across the gap between two cells.

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6
Q

Cell-Matrix, molecule involved

A

-Integrins (MANY different)

= alpha chain+ beta chain: these are binding to a part of the extracellular matrix, specifically a molecule called fibronectin.

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7
Q

how do cells actually build cell contacts or how is it that they build a way in which they can bind to the extracellular matrix? hwo do cells tick to one another?

A

-Cis + trans interactions (Velcro)

Cluster large # of CAM adjacent to one another into a patch (Velcro patch)

Cell on opposite side clusters its molecule into a patch of right size & stick together

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8
Q

Cell-cell adhesion =

A

…strengthened by adding up many weak interactions

…sort out cells of different types into clusters
-Allows cells to sort into clusters in which certain cells will only stick to ones that they like

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9
Q

sponge experiment conclusion:

A

as much as these cells like to stick to each other, there’s something about the molecules exposed on the extracellular face that is specific and that allows an orange sponge to know that it is stuck to another orange sponge, and a yellow sponge cell to know that it is stuck to another yellow sponge cell.

Something about the molecular outside is specific.

They’re not universally sticky.

They only stick to the things that are like them.

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10
Q

Cadherins can recognize…. & confer…

A

molecular fingerprint of adjacent cadherin
-Confer molecular specificity

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11
Q

Cell-cell adhesion molecules = Cadherins = …dependent

A

calcium-dependent molecules

-E-cadherins stick to N-cadherins

Cadherin transgene = cells forced to express E-cadherins

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12
Q

how did they find out cadherins are calcium-dependent molecules?

A

if you take cells and you express
a coherent trans gene (cells forced to express an E cadherin)

culture them in solutions with calcium, they will cluster together and clump.

But if you remove the calcium, they will not.

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13
Q

Cells express on their extracellular surface:

A

o Identity
o Preferred binding partners

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14
Q

Cadherins connect to … via…

A

Cadherins connect to cytoskeleton via adapter proteins

Layers of adapter proteins connect to inner face of cadherins & connect to actin

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15
Q

ECM =

A

diverse/cross-linked meshwork of polymers

Surround all our cells & tissues

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16
Q

ECM made from

A

Type IV collagen

Laminin

Entactin/perlecan

17
Q

Laminins

A

Laminin = multi-adhesive ECM protein (anchor)

Laminins (Self-assembly) – integrins
-can bind to another laminin

Laminins (Self-assembly)
-can bind to another laminin & collagen

LG domain – bind all sorts of things liekcellular receptors

18
Q

how does laminin forms the ECM?

A

take thisthis anchor shaped structure and you start cross linking it together.

And soon enough you have this big cross-linked mesh work of proteins that forms then the extracellular matrix.

19
Q

Collagen IV networks made of what kind of domains & what type of structure?

A

heterogenous polymers
-Triple helical
-N-terminal globular domain
-C-terminal globular domain

20
Q

how is Collagen IV network formed?

A

collagen for monomer: made of three polypeptide chains.

3 C terminal globular domains wound together bya triple helical structure + N-terminal globular domain can stick to each other in a tetrameric confirmation (4 of the N-terminal globular domains have stuck together with their little triple helices sticking out), globular domains can themselves dimerize = cross link network of collagen IV

21
Q

Collagen has ….. structure

A

has triple helix structure (ropes)

Single collagen polypeptide  triple helix = form triple helices ( 9 polypeptide chain)

25% of protein mass of human body = Collagen

22
Q

Collagens connect

A

tissues together

23
Q

Main challenge when producing ECMs

A

How to make these complex protein polymers inside your cells & get it outside of your cells without turning the inside into their outsides?

24
Q

solution to Main challenge when producing ECMs

A

By preventing polymerization of collagen fibers inside their ER

25
Collagen fibrils - step by step
1. Ribosomes make the collagen propeptides 2.propeptides from triple helices -collagen IV monomer 3. Folding of propeptides = procollagen -Not yet ready to polymerize & oligomerize into collagen 4. Procollagen go into Golgi complex for export & secretion 5. Lateral association of procollagen in Golgi complex -Procollagens are stacked on top of each other laterally 6. Procollagens secreted out to the extracellular space 7. Propeptide cleavage -Cell produces protease to cut off protective structures 8. Fibril assembly & cross-linking -Collagen ready to assemble
26
simple version of what they do to prevent the main problem of making ECM
prepare inside of themselves a slightly defective version capped it with protective wrapping around the sticky parts send it into the extracellular space and cut the protective cap off. can now oligomerize and polymerize.
27
Collagen fibrils prevent
collagen formation inside the cell
28
Vitamin C = cofactor in
critical enzyme that hydroxylate collagen pro-peptides in step 1
29
Scurvy caused by
by breakdown in collagen processing Vitamin C = hydroxylation of collagen pro-peptides = collagen secretion (important for wound healing)
30
* Cell-matrix adhesion molecule
integrins  straighten upon activation
31
integrins
To stick to the ECM Goes through a conformational change -Inactive/low affinity integrin = bent * When not attached to ECM -Active/high-affinity integrin = extended/straightened * Talin binding site * Kindlin binding site * Physical separation of integrin tails = mechanism of information transfer
32
How does it know that it is successfully stuck to the extracellular matrix?
inactive state: intracellular domains, alpha + beta Helix are wrapped around each other. active state: intracellular domains separated from each other physically. separation has opened up binding sites for two proteins: tailin & kindlin, now bound to the tail of that beta integrin. signal that allows the cell to know that it's stuck.
33
Integrins cluster into
focal adhesion complexes
34
Focal adhesions
feet with which cells pull on the environment layered structure
35
Focal adhesion = distinct...
5 distinct layers (like a sandwich)
36
Adhesion complexes connect to
signaling pathways Cells need to know if they are stuck to something to know how to behave Based on presence of ECM ligand binding to integrins -Affect cells decision --Divide or not Cells need to know if they're stuck to something in order to know how to behave.