Lecture 19 Cell Junctions, Cell Adhesion, and the Extracellular Matrix 1&2 Flashcards

1
Q

Anchoring junctions

A

Cell-cell adhesions and cell-matrix adhesion, and are connected to cytoskeletal filaments inside the cell

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2
Q

Occluding junctions

A

seal gaps between epithelial cells so as to make the epithelial sheet into an impermeable barrier

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3
Q

Channel-forming junctions

A

create passageways for small molecules and ions to pass from cell to cell

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4
Q

Signal-relaying junctions

A

Allow signals to be relayed from cell to cell across their plasma membranes at cell-to-cell contact

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5
Q

Cadherins have what type of binding?

A

homophilic

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6
Q

Integrins have what type of binding?

A

Heterophilic

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7
Q

Describe classical cadherin

A

Main mediators of Calcium dependent adherens junctions
also important for signaling

intracellular cytoskeletal attachement are actin filaments

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8
Q

Describe non classical cadherins

A

Desmosome junction cell to cell interaction. Used intermediate filaments for cytoskeletal attachement.

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9
Q

What are some types of classical cadherins?

A

E-, N-, VE-, P-

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10
Q

What are some types of nonclassical cadherins?

A

Desmocollins, desmogleins that form desmosome junctions

Protocadherins

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11
Q

What makes cadherins “sticky”

A

Cadherin domain motif

All cadherins have extracellular portions that contain multiple copies of cadherin domain motif

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12
Q

What end does homophilic binding occur on cadherin molecules?

A

N-terminal tips

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13
Q

What prevents the string of cadherin domains from flexing, and keeps it as a rigid rod?

What if it isnt present?

A

Ca ions bind to sites near each hinge and prevents the string from bending
When Ca is removed, the hinges can flex, and the structure becomes floppy. The N terminus changes and weakens the binding affinity and disrupts the adhesion.
Cadherins are then degraded.

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14
Q

The formation of strong attachments to other cadherins results from what?

A

Cadherins typically bind to their partners with relatively low affinity but many weak bonds in parallel functions like a Velcro to hold cells together

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15
Q

What links classical cadherins to actin filaments?

A

Intracellular anchor proteins that assemble on the tail of the cadherin.

CATENIN!!!

These proteins include β-catenin, p120-catenin, and γ-catenin (plankoglobin)

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16
Q

What are an essential part of the machinery for modeling the shape of multicellular structures?

A

Adherens junctions

Often form a continuous adhesion belt close beneath the apical face of the epithelium, encircling each of the interacting cells in the sheet

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17
Q

What lies adjacent to the adhesion belt, oriented parallel to the plasma membrane and tethered to it by the cadherins and their associated intracellular anchor proteins?

A

Contractile bundle of actin filaments

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18
Q

What is the first junction that is formed

A

cadherins = adherens junctions connected to the actin cytoskeleton

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19
Q

What cadherins forms spot well junctions in the formation in a synapse?

A

N-cadherins

allows flexibility at the synaptic cleft

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20
Q

E or N cadherins promotes migration?

A

N cadherins

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21
Q

What is similar between adherens junction and desmosomes?

A

Use cadherins

Use catenins

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22
Q

What is the difference between adherens junction and desmosome?

A

Classical cadherins and non classical cadherins

Major difference is the cytoskeletal attachment differences!!!!!
By using intermediate filaments, desmosomes can have a stronger mechanical strength

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23
Q

Bundle of intermediate filaments that are anchored to the desmosomes form a structure framework with what characteristic?

A

Great tensile strength

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24
Q

What is the structure of a desmosome?

A

Keratin intermediate filaments
Dense plaque of anchor proteins
Cadherins - Ca dependent

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25
Q

What are the desmosomal cadherins?

A

desmoglein and desmocollin

*homophilic and heterophilic binding

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26
Q

What is a desmosome mutation?

A

ARVC

sudden cardiac death in the young

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27
Q

Tight junction

A

Occluding junctions found in epithelia and endothelial sheet
Forms a seal between cells
Forms a fence between membrane domains
Recruits cytoskeleton as well as signaling molecules

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28
Q

Structure of tight junctions

A

Branching network of sealing strands
Focal connections
Proteins: claudin (main component) and occludin
*4 pass transmembrane JAMs homophilic adhesions

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29
Q

What type of junctional complexes can be found in mature epithelium?

A

Tight junction, adherens junction, and desmosome

30
Q

The positioning and organization of junctions in tight junctions in relation to other structures depends on the association with what proteins?

A

Intracellular scaffold protein of the Tip family also called ZO protein.

ZO anchors tight junctions to actin cytoskeleton

31
Q

What are three proteins that control polarization processes and maintain polarity?

A

Par, Crumbs, and Scribble

32
Q

Describe how epithelial cell polarity is established

A

Adherens junction forms and recruits Par complex.
Immediately signals to start placing tight junctions proteins right above it
Then that signals the crumbs complex to stabilize the tight junctions
Scribble comes in later for cytoplasmic proteins

33
Q

Gap junctions

A

Made up of connexins
Create a pore complex that allows things to pass between.

Channel-forming proteins

Couples cells both electrically and metabolically

Only small water-soluble molecules (mostly ions and glucose)

34
Q

Describe the hemichannel connexons in gap junction

A

Hexameric: consist of 6 connexin protein subunits

Connexins are 4 pass tmp

35
Q

A connexon can be made up of what subunits?

A

Homohexameric (same) or heterohexameric (different) subunits

Most cell types express more than one type of connexin

Humans have 14

Adjacent cells expressing different connexins can form intercellular channels in which two different join forming heterotypic

36
Q

Functions of GAP junctions

A

allow action potentials to spread rapidly from cell to cell
Syncrhonizes the contractions of heat and smooth muscle cells
Sharing small metabolites and ions by gap junctions-proiveds coordination

37
Q

Individual gap-junction channels do not remain continuously open
True or False?

A

True; instead they flip between open and closed states

38
Q

What causes gap junction channels to close immediately?

A

Large influx of Ca into the damaged cell

39
Q

Describe building of Gap Junction

A

Each gap-junctional plaque can readily assemble or disassemble. New connexons are continually added, and old removed and destroyed

40
Q

What neurotransmitter reduces gap-junction communication between a class of neurons in the retina in response to an INCREASE in light intensity?

A

dopamine

Helps the retina switch from rod to cone

41
Q

Blue represents what filament?

A

intermediate

42
Q

Red represents what filament?

A

Actin

43
Q

What layer underlies all epithelia?

A

basal lamina

44
Q

Functions of basal lamina?

A

Separates cells from connective tissue
Selective filter
Determine cell polarity
Influence metabolism
Organize proteins in adjacent plasma membrane
Promotes cell survival, proliferation or differentiation
Solid surface

45
Q

Lamina consists of what two main classes of extracellular macromolecules?

A

Fibrous protein: glycoproteins

Glycosaminoglycan: proteoglycans

46
Q

What are the compoents of basal lamina?

A

laminin, type IV collagen

47
Q

What is the primary organizer of the sheet structure of basal lamina?

A

Laminin:

Cross like structure made up of three polypeptides chains

48
Q

Type IV collagen

A

Three long protein chains that twist together to form a rope-like superhelix
Terminal domains interact to assemble network
Provide tensile strength

49
Q

What does an integrin molecule consists of?

A

alpha and beta subunits noncovalently associated

Short C-terminal tails
Large N terminal extra-cellular domains

50
Q

What is intracellular linkage to actin mediated by?

A

Talin and a set of other anchorage proteins

51
Q

What are cell-matrix attachment sites where specific type of integrin anchors the cells to laminin in the basal lamina?

A

Hemidesmosomes

52
Q

If the integrin is attached to keratin filaments, is it more likely to move or be fixed?

A

Fixed

53
Q

Contact that integrins make are often called what?

A

focal adhesions

54
Q

Describe outside-in activation and inside-out activation.

A

Outside-in: ligand attaches causing conformational change, pulls apart to allow talin to be exposed (intracellular). actin filaments assemble

Inside-out: talin brought to beta tail; breaks alpha and beta bond-activates conformation

55
Q

For cell to bind strongly to extracellular matrix requires interaction of clustering integrins. When the transmembrane portion of each type of subunit interacts with itself this is called:

A

homotypic oligomerization

56
Q

Integrins activate intracellular signaling pathways, the major protein involved is:

A

FAK: focal adhesion kinase

Src/FAK complex

57
Q

What does FAK promote?

A

cytoskeleton fluidity

Normally it helps to dissemble focal adhesions

58
Q

In most connective tissues, the matrix macromolecules are secreted largely by cells called what?

A

fibroblasts

59
Q

What are the two main classes of extracellular macromolecules that make up the matrix?

A

GAGs (creates squishiness-gel like structure) and fibrous proteins

60
Q

GAGs:

A

usually covelently linked to protein in the form of proteoglycans

forms highly hydrated, gel-like ground substance in which fibrous proteins are embedded

Provide mechanical support to tissue; withstand compressive forces

61
Q

What always comes off of the serine in a core protein in proteoglycans?

A

tetrasaccharide: serves as a primer for polysaccharide growth

62
Q

What are the four major types of glycoaminoglycans?

A

Chondrioitin sulfate,
Dermatan sulfate
Heparan sulfate
Keratan sulfate

63
Q

Sugar chains that come off of proteoglycans are always in ____

A

pairs of disaccarides

64
Q

Chondroitin 6-sulfate
Glucuronic acid
Glucosamine

A

give it to arthritic people

important components of proteoglycans

65
Q

Hyaluronic acid

A

Biggest part of proteoglycans (hyaluronic acid) composed of glucosamine and glucuronic acid

66
Q

What can be directly bound to proteoglycans that stimulate a variety of cell types to proliferate?

A

FGFs: fibroblast growth factors

67
Q

What are the most abundant protein in the body?

A

collagens

Major component of skina nd bone

68
Q

Describe collagens

A

Extremely rich in proline and glycine (helical structures and flexibility)
Long, stiff, triple-stranded helical structure

Proline forms alpha chain
Glycine allows alpha chain to pack tightly together
Left-handed helix

Twist to the left but three chains together twist right

Synthesized in the ER; secreted by fibroblast

69
Q

Type 1 collagen makes up how much of the collagen in the body?

A

90%

70
Q

Collagen diseases

A

Scurvy: lack of vitamin C

Ehlers-Danlos VI: defective enzyme-loose tissue bc of OH groups