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MCBG Exam 3 > Cell Junctions, Cell Adhesion & Extracellular Matrix > Flashcards

Cell Junctions, Cell Adhesion & Extracellular Matrix Flashcards

1
Q

What are the major differences between epithelial tissue and connective tissue

A

Epithelial tissue: very little ECM, many cells bound tightly together in sheets, cells bear most mechanical stress

Connective tissue: Mostly ECM with sparse distribution of cells, fibrous polymers are abundant, matrix bears most mechanical stress

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2
Q

What connects epithelia to connective tissue?

A

Cell-matrix attachments

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3
Q

What are the main components of cell junctions?

A

Occluding junctions, cell-cell anchoring junctions, channel forming junctions, and cell-matrix anchoring junctions

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4
Q

Describe the pattern of junctional complex adhesion molecules seen in all epithelia

A

Tight junctions are always most apical, followed by adherens junctions (actin linked) and then desmosomes (intermediate filament linked)

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5
Q

What are the main functions of tight/occluding junctions?

A

1) Permeability barrier: seal adjacent cells together
2) Regulate paracellular transport: leakage between cells
3) Fence: physically separates apical from basolateral lipid membranes

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6
Q

What proteins make up tight/occluding junctions?

A

Claudins and occludins make up the sealing strands of tight junctions

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7
Q

How does glucose pass through from the lumen of the gut to the blood?

A

Glucose is actively transported across the apical surface of the intestinal epithelia
Facilitated diffusion allows glucose to diffuse out of epithelia on the basolateral membrane

“Fence” function of tight junctions keeps these transporters separated

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8
Q

What is the clinical manifestation of misregulated paracellular transport in the intestines?

A

Fluid leaks around/between cells causing diarrhea

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9
Q

What is the function of anchoring junctions?

A

Stabilize cells against mechanical stress

Mechanically attach cells and their cytoskeleton to neighbors (cell-cell) or ecm (cell-matrix)

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10
Q

Adherens junctions connect cells to ______ via _______ proteins that are attached to cytoskeletal _________

A

Adherens junctions connect cells to NEIGHBORING CELLS via E-CADHERIN proteins that are attached to cytoskeletal ACTIN FILAMENTS

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11
Q

Desmosomes connect cells to ______ via _______ proteins that are attached to cytoskeletal _________

A

Desmosomes connect cells to NEIGHBORING CELLS via DESMOGLEIN/DESMOCOLLIN proteins that are attached to cytoskeletal INTERMEDIATE FILAMENTS

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12
Q

Focal Adhesions connect cells to ______ via _______ proteins that are attached to cytoskeletal _________

A

Focal Adhesions connect cells to ECM PROTEINS via INTEGRIN proteins that are attached to cytoskeletal ACTIN FILAMENTS

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13
Q

Hemidesmosomes connect cells to ______ via _______ proteins that are attached to cytoskeletal _________

A

Hemidesmosomes connect cells to ECM PROTEINS via INTEGRIN proteins that are attached to cytoskeletal INTERMEDIATE FILAMENTS

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14
Q

Describe the structure of adherens junctions

A

Adherens junctions join actin bundles in one cell to actin bundles in adjacent cells forming the “adhesive belt” just below tight junctions
Ca2+ dependent cadherins bind homotypically
Anchor proteins connect cadherins to actin

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15
Q

Describe the structure of desmosomes

A 
Desmosomal cadherins (desmogleins and desmocollins) link intermediate filaments between cells to give epithelia mechanical strength
Anchoring proteins = "plaque"
"Rivets" connecting adjacent cells
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16
Q

What happens in pemphigus?

A

Pemphigus is an auto-immune disease in which the body attacks its desmosomal cadherins leading to blistering

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17
Q

Describe the structure of focal contacts

A 
Transmembrane integrins (alpha/beta dimers) bind to ECM proteins allowing cells to "hang on" to surroundings
Integrins bind indirectly to actin via anchor proteins
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18
Q

Describe the structure of hemidesmosomes

A

Integrins link cells’ intermediate filaments to basal lamina via anchor proteins

19
Q

How does calcium concentration impact cadherin structure?

A

With increased [Ca2+], cadherins straighted out and are able to bind more strongly

20
Q

How do cadherin molecules facilitate cell sorting?

A

Cadherins all bind in a homophilic manner, so cells with the same types of cadherins will migrate to be next to each other

21
Q

What are the different cadherins and where can each be found?

A

E Cadherin: Epithelia
N Cadherin: Neurons, heart, fibroblasts, skeletal muscle
P Cadherin: placenta
VE Cadherin: vascular endothelium

22
Q

What are selectins?

A

Carbohydrate binding proteins that mediate cell-cell adhesion in the bloodstream
These work with integrins to allow white blood cells to slowly move through blood stream

23
Q

How do selectin and integrin allow white blood cells to enter inflamed tissues?

A
  • Selectins loosely bind to WBCs rolling along the endothelia
  • When an endothelial cell is activated by inflammatory cytokines, integrins will be expressed that will tightly bind WBCs
  • WBCs can then cross endothelia into inflamed tissue to mount immune response
24
Q

Describe the structure of gap junctions

A
  • Connexins are 4-pass transmembrane proteins that form hexamers to make a Connexon
  • Connexons on adjacent cells join to produce a functional channel
  • The permeability is dictated by the connexin composition
25
Q

How are synaptic relaying junction proteins organized?

A

Scaffold proteins organize ion channels, adhesion molecules and cytoskeletal filaments around synaptic junctions

26
Q

How is extracellular matrix produced?

A
  • Fibroblasts, chondroblasts, osteoblasts and epithelium secrete ECM
  • *ECM is made and oriented by the cells within it**
27
Q

What are GAGs?

A

Glycosaminoglycans: Unbranched polysaccharide chains made up of repeating disaccharide units (one sulfated amino sugar, one uronic acid)

  • GAGs absorb a lot of water due to high negative charge
  • Give ECM ability to resist compressive forces
28
Q

What is hyaluronan?

A

The simplest GAG

  • Very long chain (~25,000 repeats) produced by basal side of epithelial sheet
  • This produces a cell-free space into which cells can migrate
  • Can be degraded by hyaluronidase
29
Q

What are proteoglycans?

A

GAGs covalently linked to a core protein

  • Very high carbohydrate content
  • Help regulate movement of molecules and cells
30
Q

How do glycoproteins differ from proteoglycans?

A

Glycoproteins are mostly protein by weight, as opposed to proteoglycans which are mostly carbohydrate by weight

31
Q

What is the most abundant protein in the ECM?

A

Collagen makes up 25% of all protein mass in mammals and is responsible for the strength of the ECM

32
Q

Describe the structure of collagen?

A

A triple-stranded polyproline helix about 100 amino acids long
Gly-X-Y repeats where X= proline and Y=hydroxyproline
There are inter-chain H-bonds and lysine aldehyde covalent crosslinks that stabilize the coiled coil

33
Q

How is collagen synthesized?

A

Collagen is synthesized in the ER and modified in the golgi.
Within the cell, collagen exists as procollagen, a soluble form of collagen with C and N terminal peptides
Collagen is formed from procollagen in the ECM
Fibrils self-assemble into ordered collagen fiber

34
Q

What are the main types of collagen and where are they found?

A

Type I: 90% of all collagen, found in bone,skin,tendon, ligaments
Type II: cartilage, intervertebral discs
Type IV: basal lamina

35
Q

What are some examples of genetic disorder affecting collagen?

A

Osteogenesis imperfecta: defect in type I collagen causes fragile bones and weak tendons
Ehlers-Danlos Syndrom: defect in maturation/secretion of collagen type I, III, or V causes hyperflexible skin and tissues

36
Q

What is elastin?

A

A highly cross linked fiber that gives elasticity to tissues
Important in ECM of arteries
Requires fibrillin to be functional

37
Q

Which protein is affected in Marfan’s syndrome?

A

Fibrillin is mutated, which leads to decreased tissue elasticity
Large risk for aortic rupture
Skeletal abnormalities

38
Q

What is fibronectin?

A

An adhesive ECM glycoprotein that binds cells to the ECM and guides cellular migration (“track guiding cells”)
RGD sequence binds to cell integrins

39
Q

Describe the basal lamina

A

A thin, flexible extracellular matrix mat underlying epithelial cell sheets

  • Functions as a molecular filter (ex: Kidney glomerulus)
  • Important for cell orientation/polarization, cell migration, and cell survival
40
Q

What proteins make up the basal lamina?

A 
Laminin is the primary organizer of the sheet structure
Fibronectin
Type IV collagen
Perlecan (proteoglycan)
Nigoden (glycoprotein)
Heparin Sulfate (GAG)
41
Q

Describe the regeneration of the basal lamina at neuromuscular junctions

A

The junctional basal lamina mediates regeneration and tells the cell where to regenerate

-If given the chance to regenerate, nerve will form in the same place as it was before injury due to organization by the basal lamina

42
Q

Describe the structure of integrins

A

Heterodimers of alpha and beta glycoproteins that bind with low affinity to RGD sequence of ECM proteins
The cytoplasmic tail of beta subunits link to cytoskeleton

43
Q

What determines the specificity of integrin binding?

A

The combination of which alpha and which beta subunit are joined to form the functional integrin

44
Q

What are the two ways that integrin activity is regulated?

A

Inside-out signaling: inactive integrin is activated by intracellular signal
Outside-In signaling: integrin is activated by extracellular ligand leading to intracellular signaling

MCBG Exam 3 (5 decks)

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