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Phys Exam two > Cell adhesions > Flashcards

Cell adhesions Flashcards

1
Q

When dont cells operate?
When do they interact?
What is a way they interact?

A

They dont operate in isolation.
The interact to coordinate activity, direct motility, form barriers, etc.
A way they interact is through cell adhesion molecules - proteins expressed on cell surface that bind the cell to other cells

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2
Q

What are tight junctions function?
What do they do?
Where are they found?
What are they made of?

A

Epithelial barriers.
connect two cells together very tightly.
Found in epithelial layers to differentiate b/w apical and basolateral compartments.
Made of claudins and occludins (proteins)

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3
Q

What do tight junctions resemble?

A

a fence and barrier

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4
Q

What is the barrier part of tight junctions?

A

The gate - prevents (regulates) exchange b/w apical and basolateral extracellular compartments.

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5
Q

What is the fence part of tight junctions do?

A

prevents diffusion exchange of basolateral and apical membrane.

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6
Q

How can tight junctions be controlled?

A

direct action on claudins/occludins can change the permeability along with the interactions with the actin cytoskeleton.

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7
Q

What do adherens do?
Where are they found?
What are they made of?

A

Junction that causes cells to adhere to one another. Microfilament network is joined across cells.
Found in epithelial layers to provide shape and strength.
Made of cadherins anchored by intracellular catenins that attach to the actin cytoskeleton.

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8
Q

Where are adherens generally stable?
At what conditions should they be modified?
What do they interact with?
How can they be regulated?

A

Generally stable in epithelial layers, need to be modified during tissue growth or wound healing, they interact with actin cytoskeleton and can be regulated through interaction

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9
Q

Stimulus of ____ can cause contraction of_____

A

stimulus through Rho/ROCK can cause contraction of the actin cytoskeleton

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10
Q

Contraction of the actin skeleton can lead to what?

A

tension through the adherens junctions and tissue remodeling

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11
Q

Stimulus through cdc42 can lead to what?

A

removal of cadherins from the membrane and epithelial/mesenchymal transition

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12
Q

What is the name for a junction that causes cells to adhere to one another?

A

Desmosome

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13
Q

In desmosomes, what do the cells act and and what is the network that joins the cells?
Where are desmosomes found and what do they do?

A

The cells act as one mechanical unit - intermediate filament network is joined across cells
found in basal epithelial layers to give strength to the epithelium.

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14
Q

What are desmosomes made of?

A

cadherin family proteins called desmocolin and desmoglein anchored through desmoplakin to the IF network

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15
Q

Are desmosomes permanent structures?

When do they need to be remodeled?

A

yes; tissue growth, wound healing, etc

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16
Q

How are the desmosome cadherin proteins regulated?

A

through PKC phosphorylation causing stronger or weaker binding.

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17
Q

What do gap junctions allow between cells and at what part of the cell?

A

communication b/w cytoplasm of the two cells

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18
Q

What are gap junctions made of and how many?

A

Made of connexin subunits (6 on each side)

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19
Q

What do different connexins allow?

A

passage of different sizes and types of molecules

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20
Q

How are gap junctions regulated?

A

gap junction permeability can be affected by several different things, specific connexins can be added to or removed from the membrane

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21
Q

What are cadherins?

What do the bind to?

A

calcium-sensitive adhesion protein, many different cadherins, cadherins usually bind to the same cadherin

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22
Q

what are cadherins important in?

A

anchoring junctions (adherens, desmosomes), initiation of anchoring junctions, and tissue development and sorting

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23
Q

What does CAM stand for?

A

cell adhesion molecules

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24
Q

What superfamily do CAMs belong to?

A

immunoglobulin which is not calcium sensitive

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25
Q

What do CAMs bind to and what are they important in?

A

cams bind to the same cam or different proteins (homophilic or heterophilic), important in tissue sorting and immune response

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26
Q

what are selectins?

What do selectins bind to?

A

a family of cell adhesion molecules that bind carbohydrates.

Selectins bind to specific carbohydrates (or glycoprotein) on the cell surface (heterophilic)

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27
Q

What are selectins important in?

A

inflammation/immune response and uterine implantation

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28
Q

What are integrins?

A

integrins are primarily extracellular matrix binding proteins

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29
Q

What are integrins involved in?

A

cell-cell reactions

Made up of a heterodimer of an alpha-subunit and B-subunit

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30
Q

What state can integrins be in?

Can integrins bind to themselves? What can they bind to?

A

active or inactive

Integrins never bind to themselves, can bind to certain CAMs or extracellular proteins (heterophilic)

31
Q

What are integrins important in?

A

immune response

32
Q

two week old holstein calf with persistent, recurring infections
CBC - persistent neutrophilia
BLAD and Integrin B2
What do they do?

A

integrin B2 is one of the integrins integral to leukocyte attachment to epithelium. Holsteins are known to host a point mutation in CD18 that significantly lowers CD18 expression

33
Q

What would a point mutation in CD18 that lowers the expression cause?

A

This prevents leukocytes from attaching to the epithelium and leaving the blood stream to travel to sites of infection. persistent infection with persistent neutrophilia

34
Q

what happens in step 1 of Leukocyte Adhesion?

A

leukocytes have specific carbohydrates on their surface that bind P-selectin, but P-selectin is sequesteres inside endothelial cells under normal conditions

35
Q

what happens in step 2 of leukocyte adhesion

A

during inflammation, P-selectin is expressed on the surface of endothelial ells and weakly binds leukocytes, causing the leukocyte to roll along the surface

36
Q

what happens in step 3 of leukocyte adhesion

A

other inflammatory signals cause activation of leukocyte function associated antigen (LFA) on the leukocyte

37
Q

what happens in step 4 of leukocyte adhesion

A

LFA strongly binds to ICAM-1 slowing down the leukocyte and allowing diapedesis into the tissue

38
Q

Presentation - 7 y/0 boxer with swelling around gums, excessive salivation, coughing, reduced appetite. examination - swollen areas are highly pigmented, teeth are loose, lymph nodes in the area are swollen. FNA - of mass and lymph nodes shows pigmented neoplastic cells
X-ray - dense masses in lung
Diagnosis?

A

oral melanoma

39
Q

What secretes ECM?

A

groups of cells organize the environment around them and secrete ecm.

40
Q

What is ECM?

A

a collection of fibers that support and connect the cells and integrate tissues

41
Q

What is ECM made up of (3 components)? Do different tissues have the same ecm?

A

made up on protein fibers, complex carbs, and cell-matrix adhesions. different tissues have different ECM (example - bone vs liver)

42
Q

Collagen in ECM - what is the structure?

A

fibrous, helical proteins that can be oriented in parallel or obliquely to create strength in different dimensions. Different collagens w/ differential expression

43
Q

What does collagen do and what is the ECM strength and rigidity influenced by?

A

Collagen gives strength and rigidity which is influenced by type of collagen, amount of collagen, cross-linking, and orientation.

44
Q

What do we have to introduce to create the triple helix of collagen?

A

introduce new aa (hydroxyproline – allows kink to form in the collagen chain so we get the triple helix).
We start with proline and introduce vitamin C (redox reaction), we oxidize the proline and use the oxidized vitamin C to make hydroxyproline.
If we don’t have vitamin C, it won’t fold properly.
Collagen is the major fiber

45
Q

Elastin in ECM, what is it? How is its structure when relaxed vs tensed?

A

Fibrous, relatively disordered protein. Relaxed - highly coiled. Tense - causes the fibers to straighten.

46
Q

Structure and function of elastin in ECM

Where is elastin important?

A

highly cross-linked which confers memory on the matrix, gives flexibility to the ECM, important in lung, large arteries, skin, intestines, etc.

47
Q

What are glycosaminoglycans aka GAGs?

A

long polymers of repeating sugar units and are usually significantly negatively charges

48
Q

What are proteoglycans?

Are large portion of what of ecm?

A

fibrous proteins with GAGs attached

large portion of VOLUME

49
Q

Most of ECM mass is made up of what?

A

protein content

50
Q

What are most GAGs found as?

A

proteoglycans, except hyaluronan

51
Q

GAGs hold a lot of what?

A

water

52
Q

The concentration and make up of GAGs/proteoglycans can affect what?

A

movement of water and solutes in a tissue

53
Q

Do GAGs have a charge? If so, what does it do?

A

yes; they are highly charged and repulse each other, giving volume and resistance to compression

54
Q

Can GAGs function as signaling molecules?

Example?

A

yes; and have complicated interactions with cells.
Example - HA can act as migration substrate and a signal for epithelial mesenchymal transition for migratory cells esp. in embryonic development

55
Q

What is HA production and signaling controlled by?

A

hyaluronan synthases and hyaluronidases

56
Q

Where are GAGs found?

A

throughout the body but important in cartilage,

57
Q

A (high/low) concentration of (highly/lowly) charged GAGs turns cartilage into what?

A

high, highly, turns cartilage into stiff water balloon that cushions the joint. Chondroitin sulfate

58
Q

Other GAGs act as…

A

oil, absorbing water and turning into a viscous liquid that lubricates the joint (hyaluronic acid)

59
Q

What two families of adaptor proteins link the ECM in the cell?

A

Laminins and fibronectins

60
Q

What are laminins made up of?
What do they bind to?
What does it crosslink?
Especially present in what?

A

three strands with a triple helix structure. Binds to collagen 4, some GAGs and to cell surface receptors.
Crosslinks the matrix and connect to the cell.
Present in Basal Lamina

61
Q

What are fibronectins made up of, what do they bind to, what do they crosslink?

A

made up of two strands, binds to collagen, some gags, some proteoglycans, and to cell surface receptors.
Crosslinks the matrix and connects to the cell.

62
Q

What are integrins?

What can they attach to?

A

Transmembrane proteins that bind to fibronectins or laminins to attach the cell to the ECM.
can attach to the cytoskeleton through adapter proteins.

63
Q

What do integrins facilitate?

A

communication and cohesion b/w the intracellular matrix and EXM

64
Q

What are focal adhesions made of?
What attaches to their matrix?
Where are they found?

A

Made up of integrins bound to actin filaments.
Similar to adheren junctions with integrins attaching to the matrix.
Found in non-epithelial cells, especially migrating cells, can be very dynamic adhesions

65
Q

What are hemidesmosomes made of? What attaches to their matrix? Where are they found?

A

Made of integrins bound to intermediate filaments, similar to desmosomes with integrins attaching to matrix. Found primarily in epithelial cells, often very stable adhesions.

66
Q

How can cells remodel the ecm?

What is a main factor of remodeling?

A

Can remodel the ecm by digesting the current ecm and secreting new ecm. Main factors in ecm degradation and remodeling are the matrix metalloproteases (MMPs)

67
Q

What can digest specific ECM components and when?

A

Different MMPs can digest specific ECM components when activated by the cell.

68
Q

When are MMPs expressed?

A

During wound healing, and migration (especially immune cells)

69
Q

Presentation - 7 y/0 boxer with swelling around gums, excessive salivation, coughing, reduced appetite. examination - swollen areas are highly pigmented, teeth are loose, lymph nodes in the area are swollen. FNA - of mass and lymph nodes shows pigmented neoplastic cells
X-ray - dense masses in lung
Diagnosis and prognosis

A

Stage 4 oral melanoma w/metastasis in lung

Prognosis - average survival time of only 65 days

70
Q

What has to happen fo r the tumor cells to migrate away from the primary tumor?

A

ECM has to be remodeled

71
Q

What does the basal lamina need to be changed into?

A

it is a dense meshwork of fibers, needs to be changed into straight paths of collagen fibers that the cell can migrate down

72
Q

MMPs and Oral melanoma

What specific MMPs had increases in early and late OM?

A

several MMPs may be overexpressed and mis-regulated in canine oral melanomas, MMP2 mRNA had 90x increase over normal controls in early stage OM and 30x in late stage, MMP14 had a 5x in early and 3x in late

73
Q

What contributes to the extreme metastatic potential of OM?

A

the mis-regulation of ECM remodeling

Phys Exam two (13 decks)

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