Epithelial Structure Flashcards
Xeroderma pigmentosum
defect in DNA repair, DNA repaired via nucleotide excision repair
UV sensitivity syndrome (UVSS)
disrupted desmosomes in basal keratinocytes
Connective Tissue
directly bears mechanical stresses of tension and compression
bones and tendons
plenty of ECM and sparse cells
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
Cell to cell anchoring junctions
adherens junction
desmosomes
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
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
Tight junction
seals apical membranes, cell polarity is key
gap between epithelial cells
discretion of tight junction
uses 4 pass membrane proteins
- Claudin and 2. Occludin
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
Classical adherins
homophilic
e-cadherin
cytoskeleton association: actin filaments via catenins
cell junction association: adherent junctions (cell to cell connection), synapses
Desmosomal adherins
homophilic
Desmoglein and Desmocollin
cytoskeleton association: intermediate filaments
cell junction association: desmosomes
Integrins
heterophilic
many types
cytoskeleton association: actin filaments,
bind to ECM but not other integrins
cell junction association: focal adhesions (found in hemidesmosomes)
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
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
Intermediate filaments
(think girders in a building)
provide mechanical strength beause they are strong filaments
resist mechanical stresses
keratin
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
Actin filaments
determine cell’s surface
necessary for whole-cell locomotion, secretion, and endocytosis
accessory protein: Arp!!!!!!
Fibroblasts
make ECM proteins and tissue that epithelial cells sit on
Extracellular Matrix (ECM)
secreted by fibroblasts –> provide mechanical support
Blood vessels
lined with endothelial cells (polarized)
- supply nutrients and oxygen
- remove waste
Skin
Contains:
- ECM
- Blood Vessels
- Macrophages and dendritic cells
- Lymphocytes
- nerve fibers
- Basal Stem Cell***
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,
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 turgorEpidermis
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
Epidermis Layers
From top down:
- keratinized squames, made of keratinocytes
- granular cell layer, waterproof barrier
(also a barrier between inner active layer and outer dead epidermis) - Prickle cell layer
- Basal cell layer, attaches to the basal lamina. these are the only dividing cells in the epidermis
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)
Transmembrane adhesion proteins
2 families:
Cadherins: cell to cell connection
Integrins: attachment of cells to matrix
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)
Anchor proteins
Beta-catenin,
p120-catenin,
gamma-catenin
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
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
Cytoskeleton
important in cell motility
guides intracellular traffic
includes motor proteins
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
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
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
Synthetic triterpenoids
drugs that target ARP by inactivating the G-protein
good at stopping metastasis
also blocking RTK pathway will prevent ARP
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
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
Collagen
3D shape comes from 3 monomer strands
very rich in proline and glycine
most common is 1, 2 and 3 types
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
Non-fibrillar collagen
Types 9 and 12
structure of planar basement membranes
anchoring fibrils to basement membrane beneath the squamous epithelium
Postranslational Hydroxylation
Proline and lysine hydroxylation via:
prolyl and lysyl hydroxylases
need vitamin c (ascorbic acid) for function of enzymes
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
Scurvy
loss/deficiency of cofactors Vit C and Fe2+
prolyl hydroxylase affected
Sx: wounds reopen, loses teeth, pale skin,
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
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
chondroitin 6 sulfate
arthritis, joint relief
pharmaceutical treatment
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
