Epithelial Structure Flashcards Preview

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Flashcards in Epithelial Structure Deck (47):
1

Xeroderma pigmentosum

defect in DNA repair, DNA repaired via nucleotide excision repair

UV sensitivity syndrome (UVSS)

disrupted desmosomes in basal keratinocytes

2

Connective Tissue

directly bears mechanical stresses of tension and compression

bones and tendons

plenty of ECM and sparse cells

3

Epithelial Tissue

polarized

mechanical stresses transmitted from cell to cell by cytoskeletal filaments

cytoskeleton of cells linked from cell to cell by anchoring junctions

ECM is scanty, just thin basal lamina

4

Cell to cell anchoring junctions

adherens junction

desmosomes

5

Adherens junction

cadherins, catenins, and actin
-connect actin bundle from one cell to the next one

-actin-linked cell matrix adhesion anchors actin filament in cell to the ECM

e-cadherins: transmembrane adhesion molecules associated with cell motility and shape

6

Desmosomes

anchoring junctions, attach cells and cytoskeletons to other cells and or to the ECM by using intermediate filaments

found in heart and skin (high stress/tension tissue) because they provide mechanical strength

spot-welds
Ca+ dependent

spot desmosome: between cells
hemidesmosome: bind to ECM

uses cadherins: 1. Desmoglein 2. Desmocollin

7

Tight junction

seals apical membranes, cell polarity is key

gap between epithelial cells
discretion of tight junction

uses 4 pass membrane proteins

1. Claudin and 2. Occludin

8

Gap junction

creates a pore

allows passage of small water soluble molecules between cells

Connexins: channel forming protein

Couples cells electrically and metabolically (signal transduction and signal depolarization)

important in cell to cell communication

9

Classical adherins

homophilic

e-cadherin

cytoskeleton association: actin filaments via catenins

cell junction association: adherent junctions (cell to cell connection), synapses

10

Desmosomal adherins

homophilic

Desmoglein and Desmocollin

cytoskeleton association: intermediate filaments

cell junction association: desmosomes

11

Integrins

heterophilic

many types

cytoskeleton association: actin filaments,

bind to ECM but not other integrins

cell junction association: focal adhesions (found in hemidesmosomes)

12

Desmosome mutations

Mutation in Desmocollin-2 is associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)

common cause of sudden death in the young

desmosome is not properly inserted in membrane

13

Blistering Disorders

Some autoimmune responses react to desmosome cadherins such as desmoglein 1 and 3

desmoglein 1 in epidermis

desmoglein 3 in spinous layer

desmoglein 1 Attacked by antibodies results in pemphigus foliaceus

14

Intermediate filaments

(think girders in a building)

provide mechanical strength beause they are strong filaments

resist mechanical stresses

keratin

15

Microtubules

(slinky of life)

tube like structures, determine positions of organelles and direct intracellular transport

staggered tetramer of 2 coiled-coil dimers

make up centrioles and mitotic spindles

accessory protein: Tau

16

Actin filaments

determine cell's surface

necessary for whole-cell locomotion, secretion, and endocytosis

accessory protein: Arp!!!!!!

17

Fibroblasts

make ECM proteins and tissue that epithelial cells sit on

18

Extracellular Matrix (ECM)

secreted by fibroblasts --> provide mechanical support

19

Blood vessels

lined with endothelial cells (polarized)
-supply nutrients and oxygen
-remove waste

20

Skin

Contains:
1. ECM
2. Blood Vessels
3. Macrophages and dendritic cells
4. Lymphocytes
5. nerve fibers
6. Basal Stem Cell***

21

Basal stem cell

responsible for generating tissue in the basal layer
(doesn't make macrophages)

responsible for integrity of the whole tissue, connected to connective tissues

talks to fibroblasts,

22

Skin layers

Epidermis
– Forms the outer covering of skin
– Creates a water barrier
– Made of epithelial cells
– Continuously repaired and renewed
Dermis
– Second layer
– Rich in collagen
– Provides toughness
Hypodermis
– Fatty subcutaneous layer
- greatly affected by dehydration-skin turgor

23

Epidermis

renewed every 30 days by basal cells (stem cells)

stem cells create 2 cells:
-one identical cell
-one cell that differentiates into something specific

changes some desmosomal proteins and some keratins at each layer

24

Epidermis Layers

From top down:

1. keratinized squames, made of keratinocytes

2. granular cell layer, waterproof barrier
(also a barrier between inner active layer and outer dead epidermis)

3. Prickle cell layer

4. Basal cell layer, attaches to the basal lamina. these are the only dividing cells in the epidermis

25

Stem cell

primitive cell that can self-renew or give rise to more specialized cell types

ex: one blood stem cell can give rise to red cells, white cells, and platelets

can divide without limit: telomerase

Adult stem cells are tissue specific
(skin basal stem cells are adult)

26

Transmembrane adhesion proteins

2 families:

Cadherins: cell to cell connection

Integrins: attachment of cells to matrix

27

Cadherin-Mediated Adhesion

highly selective recognition

enable cells of similar types to stick together and segregate from other cells

if you lose epithelial cadherin (E-cadherin) you lose the cell to cell connection

E to N cadherin switch is important in early development

but... E to N switch is mimicked in metastasis later on (breast cancer)

28

Anchor proteins

Beta-catenin,

p120-catenin,

gamma-catenin

29

Beta Catenin

also a transcription factor

when Wnt-1 binds to receptor

B-catenin travels to the nucleus from an e-cadhedrin

this then begins Wnt1 genes to be expressed (bad)

big in cancer signaling

30

B-catenin mutation to cancer

common mutation

over expression and cell proliferation

inhibits APC (tumor suppressor)

RAS is activated (oncogene)

other tumor suppressors inhibited including p53

31

Cytoskeleton

important in cell motility

guides intracellular traffic

includes motor proteins

32

ARP (ARP 2 and ARP 3)

accessory protein to actin

important in movement

70 degree angle from mother cell

activates formation of actin polymerization and thus cables get built

as these cables push forward you get protrusion of membrane and movement of the cell

33

Listeria

presents on surface protein called ActA

ActA then activates ARP 2/3 complex

causes the toxin to be pushed around on cables and migrates

34

Cell migration by external signals

Rho and Rac are both small G proteins (monomeric, Cdc42 as well)

active with GTP and inactive with GDP

an external chemoreceptor causes G-alpha-I to inhibit AC and then forces PIP2 to form Rac instead of dissociating

this then activates ARP which causes polymerization of actin and thus protrusion (movement of cell)

Rho is activated as well and causes contraction (actin-myosin contraction) at the back of the cell to allow continued cell movement

35

Synthetic triterpenoids

drugs that target ARP by inactivating the G-protein

good at stopping metastasis

also blocking RTK pathway will prevent ARP

36

Integrin downstream signaling

Src/FAK activate ERK and JNK to regulate cell proliferation, cell survival, and differentiation

SFK: Src family kinase = activates Grb2 for RTK pathway to get to ERK

37

Laminin

connects many different components together

most abundant ECM protein in basement membrane

connects cells to ECM components, especially type 4 collagen (network forming collagen)

also modulates cell proliferation, differentiation, and motility

38

Collagen

3D shape comes from 3 monomer strands

very rich in proline and glycine

most common is 1, 2 and 3 types

39

Fibrillar collagen

Types: 1, 2, 3, 5
stabilized by H bond

major portion of connective tissue and wound healing

strength comes from covalent bonds using lysyl oxidase which requires VIT C**

diseases can result:
osteogenesis imperfecta
Ehlers Danlos syndrome

40

Non-fibrillar collagen

Types 9 and 12

structure of planar basement membranes

anchoring fibrils to basement membrane beneath the squamous epithelium

41

Postranslational Hydroxylation

Proline and lysine hydroxylation via:

prolyl and lysyl hydroxylases

need vitamin c (ascorbic acid) for function of enzymes

42

Ehlers Danlos syndrome

a decrease in lysyl hydroxylase (enzyme) leads to overly flexible joints, blood vessel walls, uterus,

Vitamin C needed for this enzyme function

43

Scurvy

loss/deficiency of cofactors Vit C and Fe2+

prolyl hydroxylase affected

Sx: wounds reopen, loses teeth, pale skin,

44

Elastin

ability of tissues to recoil and recover shape

important in cardiac valves

stretching exposes hydrophobic regions, relaxing covers

at the core of fibrillin filaments

defect in fibrillin leads to Marfan's syndrome, Mitral valve prolapse, and aortic aneurysm

45

Proteoglycan

extracellular molecule made of proteins and sugar

fibrous structural protein, binds to protein growth factors

heparan sulfate attaches to fibroblast growth factor (FGF) and causes proliferation

TGF-beta (transforming growth factor-beta) binds to proteoglycan decorin which inhibits growth factors

made of long polypeptides called glycosaminoglycans (GAGs)

synthesized by repeating disaccharides, hundreds of sugars in one strand

46

chondroitin 6 sulfate

arthritis, joint relief

pharmaceutical treatment

47

Hyaluranon

long repeating sequence of gluconic acid and acetylglucosamine

provides mechanical support to tissues

attracts a lot of cations (Na+) and draws in water to matrix to help withstand pressure