10.1 Cell Adhesions

Question 1

What are cell-adhesion molecules or CAMs?

Answer 1

CAMs help cells adhere to other cells or matrix. They perform structural roles but also provide cells with information about their surroundings and neighbors. the attachment of cells to each other is a reflection of active decisions made by cels

Question 2

How are adhesion molecules divided?

Answer 2

Into two groups: those that require extra cellular calcium (can be further divided into three groups) for their function and those that do not require calcium.

Question 3

What are the three groups that calcium dependent adhesion molecules can be divided into?

Answer 3

1) Selectins (L, P, and E selectins)
2) Integrins
3) Cadherins

Question 4

What do selectins bind to? Is their attachment strong or weak?

Answer 4

selectins are molecules that bind to carbohydrates found on other cells or in the extracellular matrix and they do so in a calcium dependent manner.

Their adhesions are the weakest type of attachment and they are used to form temporary and weak attachments.

Question 5

Where are L selectins found?

Answer 5

found on white blood cells or Leucocytes

Question 6

Where are E selectins found?

Answer 6

found on endothelial cells

Question 7

Where are P selectins found?

Answer 7

on both white blood cells/leucocyts or endothelial cells.

The P stands for platelet.

Question 8

What are lectins?

Answer 8

proteins that bind to sugars or carbohydrates

Question 9

What is a C lectin

Answer 9

lectin proteins that have a trans membrane tail which anchors them to the actin cytoskeleton on the intracellular side of the cell membrane.

Question 10

What do endothelial cells do when tissues initiates an inflammation response?

Answer 10

endothelial cells express E and P selectins during inflammation to recruit white blood cells with L-selectins.

Question 11

In the inflammation response, what happens after epithelial cells begin to express P selectins on their surface?

Answer 11

Circulating white blood cells (L-selectins) will bind to the end of the endothelial cells (they bind b/c both cells express compatible glycosylated proteins on their surfaces.

Question 12

What kind of bond (strong or weak) does selecting create between epithelial cells and white blood cells in inflammation response? What does this attachment type result in?

Answer 12

Selectins create a weak bond. The weak binding are not strong enough to anchor white blood cells against the blood flow but strong enough to attach the white blood cells to the vessel wall.

This results in a highly characteristic of rolling behavior of white blood cells in the area of an inflammation.

Question 13

Why is the rolling behavior of white blood cells in an area of inflammation important?

Answer 13

this behavior is going to allow the white blood cells time to organize and activate other and stronger adhesion molecules.

once the stronger adhesion molecules are activated leukocytes exit the blood vessels and enter the surrounding tissue

Question 14

What would happen if white blood cells did not exhibit rolling behavior in inflammation response? And if they had a strong attachment?

Answer 14

If white blood cells had a very strong adhesion molecule activated all the time they would just exit the blood stream randomly and wouldn’t exhibit this sort of homing behavior.

Question 15

What happens if selectins are not present in cells?

Answer 15

resistance to infection decreases.

Question 16

What happens if a tumor cell expresses selectins?

Answer 16

the cells enhances metastasis

Question 17

What is the structure of integrins?

Answer 17

heterodimers made up of an alpha and beta subunit. They contain extracellular adhesion domains as well as a trans membrane helix and a intracellular tail that is used to anchor the integrin’s to the actin cytoskeleton.

Both subunits have calcium binding domains and the calcium is needed to allow the integrin’s subunits to have the right shape for attachments.

Question 18

What are integrins responsible for?

Answer 18

adhesion to specific extracellular matrix components.

Question 19

What does the cytoplasmic tail of integrin bind to?

Answer 19

to actin bundling proteins like filament, talin, and alpha actinin

Question 20

When integrins cluster they form what?

Answer 20

focal adhesions

Question 21

What are focal adhesions kinase (FAK)?

Answer 21

FAK phosphorylates integrins

Question 22

What happens to the cell in the absences of FAK?

Answer 22

the cells (non motile cells) form abnormally high number of focal adhesions, which are very stable.

Question 23

Why is phosphorylation of integrin required in a cell? What phosphorylates integrin?

Answer 23

Phosphorylation is required in order to allow focal adhesions to reorganize and disassemble.

FAK phosphorylates integrins.

Question 24

What happens to a cell in the absence of activated Rho?

Answer 24

no focal adhesions form.

Question 25

Where do FAKs interact with integrins? What happens if integrins are clustered when they are phosphorylated by FAK?

Answer 25

in focal adhesion complex.

FAK proteins can phosphorylate other FAK molecules, initiating FAK dependent intracellular signaling events.

Question 26

How is the formation of integrin clusters facilitated?

Answer 26

They are facilitated if the amount of a specific extracellular matrix component is especially high in a small area b/c a specific extracellular matrix type of molecule will be recognized and bound by a specific integrin heterodimer.

This allows cells to have information about what kind of extracellular matrix molecules are present in their environment.

Question 27

What are Cadherins?

Answer 27

a super family of related proteins that form strong and stable attachments between cells.

The cadherin family has many variations each of which is used by cells to attach to a unique set of targets

Question 28

What role does the diversity of cadherins play?

Answer 28

plays a role in development and tissue maintenance

Question 29

What is unique about the gene structure of cadherins?

Answer 29

each gene contains a few constant regions that will appear in all the cadherin proteins expressed by that gene. As well as a large number of varial regions. This particular gene has 15 variable regions. Gene splicing events will result in the inclusion of only 1 of the variable regions in the final protein and therefore this one gene can be used to create up to 15 different gene products each with unique adhesion characteristics and tissue distribution patterns.

Question 30

What is the structure of cadherins?

Answer 30

homodimers with single pass transmembrane anchoring domain and an extracellular domain (which bind calcium) with 5 or 6 cadherin repeats. The repeat domains are structurally related to immunoglobulins.

Question 31

What links cadherins to the actin cytoskeleton?

Answer 31

catenins

Question 32

What is a difference between integrins and cadherins?

Answer 32

Cadherins are homodimers whereas integrins are heterodimers and cadherins uses catenins to link themselves to the actin cytoskeleton

Question 33

What are the three classes of cadherens?

Answer 33

1) P-cadherins (placenta and epidermis)
2) E cadherins - epthielial
3) N-cadherins (neurons and muscles)

Remember PEN

Question 34

How does calcium regulate cadherin junctions?

Answer 34

calcium maintains the shape of cadherin dimmers. In the absence of calcium the structure of cadherins collapses (become floppy and don’t attach to neighboring cells)

Calcium binds to multiple sites along the adhesions domains of cadherins and this straightens and stiffens the molecule. This stiffness allows homotypic interaction of cadherins from apposing cells.

Question 35

What is the function of cadherins?

Answer 35

cadherins mediate cell-cell attachment by homotypic interactions. They are associated w/ adherens junctions. Mixed cells with different cadherins can sort into 2 populations by adhesions type or strength.

They play a central role during embryo genesis!

Question 36

Describe the experiment that helped determine that cadherins play a role in develpment (embryo genesis)

Answer 36

1) different types of cells where mixed together in a culture and then the culture was shaken or stirred over night.
2) The resulting clumps of cells were generally not randomly organized
3) instead some cells would be found in an inter-mass (inner endothelial cells) and other found in a peripheral layer (outer epithelial cells).
4) The position of cells w/in the cluster could be predicted by the strength of cell to cell adhesions.

Question 37

Lack of N-cadherins during development can lead to what?

Answer 37

neural tube defects and absence of the fold between the fore brain and the hind brain.

Question 38

Why might adhesion be down-regulated during embryo development? What is an example of this?

Answer 38

The loss of attachment of cells to each other also play important roles in development and cadherins are involved in these event.

EXAMPLE: the movement of cells out of the developing neural tube structure of an embryo. Certain cells (neural crest cells) develop in the top/dorsal side of the neural tube, which goes on to form the brain and spinal cord. however, neural crest cells leave the tube and participate in formation of nerve, muscle, pigment and bone cells in other regions of the body.

In order to leave the tube, these cells must down regulate the expression of cadherins. Failure to down regulate can cause defects in this development of those other tissues.

Question 39

What is the structure of CAMs (cell adhesions molecules)?

Answer 39

These proteins have five globular regions in their extracellular domains that closely resemble similar parts of antibody molecules.

These domains are therefore known as immuno-globulin or IG-like domains.

Question 40

What type of binding do CAM IG-like domains form?

Answer 40

these domains form homotypic binding interactions, meaning they will bind to an identical molecule expressed by another cell.

Question 41

What are the two kinds of CAMs?

Answer 41

1) N-CAMs (neurons

2) I-CAMs (endothelial cells)

Question 42

What is the difference between N-CAMs and I-CAMs?

Answer 42

N-CAMs are monomeric, while I-CAMs are dimers.

They also are expressed in different cells N=neurons and I=endothelial.

Question 43

What type of adhesions do CAMs form?

Answer 43

not very strong adhesions and not calcium dependent. But they play an important role in guiding the adhesions of cells which may then form stronger attachments at a later time. In this way, their role is somewhat similar to that of selectins

Question 44

What is the role of N-CAMs? What happens to cells that are N-CAM deficient?

Answer 44

they form junctions between nerve and muscle cells.

N-CAM deficiency can lead to smaller and less elaborate neuromuscular junctions although the junctions still form to some extent. SO N-cams fine tune the attachment of cells to each other.