Structure of Epithelia Flashcards
What is a common quality of epithelial cells
they interface with external environment
Characteristics of epithelial cells
- have an apical and basolateral face
- have specialised structures that can sense a mechanical disturbance in the environment
- can interface between an environmental stimulus and NS
- have neural epithelial function
What is an epithelia
- animal tissue composed of cells packed into sheets by forming polarised apical and basolateral domains
- cells sit parallel to one another attached to thin fibrous basement membrane
- lines surfaces of cavities and structures in body
- sheets lack blood vessels but contain nerves allowing neural contribution to sensation, absorption, protection, and secretion
- in development, they act in conjunction with one another to form and maintain organs throughout life
Shapes of epithelial cells
- cuboidal (cube)
- columnar (rectangular)
- squamous (flat (e.g. skin))
Layers of epithelial cells
- simple epithelium (single layer)
- stratified epithelium (several layers)
- pseudo-stratified epithelium (one layer, varied heights (e.g. in lungs))
Specialised forms of epithelial cells
- ciliated (primary cilia, motile cilia)
- neural connections (neuroepithelial cells)
- mucus-secreting (goblet cells)
Example of squamous epithelial cell in lung alveolus
Alveolar type-I cells
- surface area for gas exchange
Capillary endothelium
- capillary wall
- surface area for gas exchange
Examples of cuboidal epithelial cells in lung alveolus
Alveolar type-II cells
- fluid secretion (airway surface liquid)
- surfactant secretion (mechanical support)
- stem cells for AT-I cells
Epithelial functions of lung bronchial airway
- fluid secretion (airway surface liquid)
- mucus secretion (particle clearance)
- motile cilia
- pathogen defence
Epithelial functions of lung neuroepithelial bodies (innervated epithelium)
- chemosensing and regulation of breathing
Epithelial functions of kidney nephron and collecting duct (cuboidal secretory epithelium)
- ion transport
- fluid homeostasis
- hormone secretion (renin, erythropoietin)
- acid base balance
Epithelial functions of gut mucosa (simple columnar epithelium with goblet cells)
- ion transport
- fluid homeostasis
- mucus and digestive enzyme secretion
- nutrient absorption
Endothelial interactions in the blood-brain barrier
- endothelial:astrocyte interactions
- ion transport
- fluid homeostasis
- selective hormone signalling
Epithelial functions of innervated sensory epithelium of the ear (ciliated neuroepithelial “hair” cells)
- mechanosensing
- neuro transduction
Epithelial functions of retinal photoreceptors of the eye (neuroepithelium with highly modified cilium)
- photoreception
- neurotransduction
Why is polarity crucial for function
- gives direction to transport of ions and nutrients (e.g. vectored transport)
- specialisation of function at one end of the cell or another (e.g. retinal cells, hair cells)
- supports formation of complex architectural shapes (e.g. branching morphogenesis)
- loss of polarity leads to disease
Which order do epithelial cell junctions aquire apical-basolateral polarity
1) adherens junction
2) tight junction
3) desmosome junction
4) gap junction
5) hemidesmosome junction
Which order do epithelial cell junctions appear anatomically
1) tight junction
2) adherens junction
3) desmosome junction
4) gap junction
5) hemidesmosome junction
The adherens junction
- responsible for cell-cell recognition
- primitive contacts made through homophilic Epithelial Cadherin Interaction
- F-Actin bundles are diffused
- binds cells together
What are cadherins
- cell adhesion proteins
- fundamental for multi-cellular life
- Ca2+-dependent homo-dimerisation between extracellular domains holds cells in contact
- carboxy-terminus is anchor for p120, alpha, beta, and gamma Catenin
- cell-cell binding using E-Cadherin causes actin bundles to organise themselves around intracellular domain of junction to stabilise it
p120 Catenin
- prototypical isoform
- stabilises adherens junction
- initiates formation of other junction complexes
alpha-Catenin
- forms homodimer that anchors actin filaments to membrane
beta-Catenin
- released from E-Cadherin by proteolysis
- acts as nuclear signal to stimulate loss of polarity and cell growth
- has a dual role -> when free it goes to nucleus and acts as TF to bind TTF/Lef1 domain (stimulates cell cycle, metastasis cue)
gamma-Catenin (Plakoglobin)
- alters type of junction complex and is common to desmosomes
What is role of Catenins
- bind F-Actin and build cytoskeletal structures
Function of adherens junction
- anchors F-Actin
- F-Actin forms supporting belt structure around inner cell membrane
- supports transition to cuboidal structure and recruits other cytoskeletal elements (eg tubulin)
How do junction complexes stabilise cell structure
- inhibiting cell passage by sequestering key transcription factors
- beta-Catenin provides an example of this
The tight junction
- seals apical and basolateral membranes
- tight junctions form of the apical side of Adherens junction and creates impermeable barrier
- blocks paracellular movement and acts as fence to separate apical and basolateral membranes
- make basolateral membranes distinct from one another
Basic unit of tight junction
Occludin
Formation of barrier and fence
- homodimerization of Occludin extra-cellular domains forms impermable seal between cells (barrier)
- transmembrane Occludin domains separate apical and basolateral membranes (fence), preventing movement of proteins between membranes
Function of zona occludens proteins
anchor cytoskeletal proteins to the tight junction complex
Proteins involved in tight junctions
- ZO-1
- ZO-2
- ZO-3
- Actin
- Myosin
Role of Phosphoinositide-3-Kinase (PI3K) and PTEN
- PTEN is PI3K inhibitor
- regulate phosphoinositide (PtdIns) content of apical and basolateral membranes
- acts as recognition signature for protein transport to either membrane
Role of Par3 in tight junction
recruits PTEN to tight junction
Role of PTEN in tight junction
enriches PIP2 in apical membrane
Role of PI3K in adherens junction
enriches PIP3 in basolateral membrane
The desmosome
- resist mechanical stretch and shear
- form loose junctions between cells and enable cell shape to distort without tearing during mechanical strain
Desmosomal junctions (macula adherens)
- composed of cadherin-family proteins (desmoglein, desmocollin) which are anchored in the membrane by plakoglobin and plakophilin heterodimers
Role of desmoplakin
binds desmin (cytoskeletal protein) to desmosome junction complex
Consequences of weakened desmosomes
- intraepithelial lesions within epithelial tissue
- pemphigus vulgaris
The gap junction
- connects epithelial cells as a syncitium
- formed from hexamers of connexin proteins
- function as channels that connect cytoplasm of one cell to another
- establish lateral or Planar Cell Polarity (PCP)
Structure of the gap junction
- 6 connexins form hemi channel
- extracellular connexin loops link hemi channels between neighbouring cells
- channel pore facilitates electric and metabolic coupling between cells
Describe the bystander effect
- death of one cell (e.g. by viral infection) spreads as a signal to neighbouring cells and limits spread of infection by creating a ‘zone of cell death’
The basement membrane
- provides structural support
- extracellular matrix underlying all epithelia connecting cells to connective tissue
- composition influences cell metabolism, survival, proliferation, migration
Main components of the basement membrane
- laminin: primary organiser of BM proteins and forms Lamina densa
- integrins: expressed on basolateral side of cell and form Lamina lucida, and binds to laminin
- collagens and fibronectin: chicken-wire-like meshwork that gives BM tensile strength
- Nidogen and Perlecan: link laminin to collagen and fibronectin
How does cell attachment between basolateral and basement membranes occur
through integrins
Mutations in the hemidesmosome (basement membrane)
epidermolysis perlosia (affects ability of lamanin to bind to collagen)
Loss of epithelial structure: cancer
- loss of cell polarity disrupt cell junctions and promote cell growth and migration (loss of FENCE)
- e.g. mutations can disrupt association of PTEN with Par3 in tight junctions
- loss of PIP2/PIP3 signature of apical and basolateral membranes disrupts intracellular trafficking and polarity
- degradation of E-Cadherin releases beta-catenin which enters nucleus and increases cell growth by activating LEF-1/TCF driven expression of cell cycle genes
Loss of epithelial structure: Gluten intolerance / Crohn’s disease
- activation of auto-immune response which disrupts tight junction barrier function, enhancing pathological paracellular transport
- gluten stimulates zonulin secretion from gut -> opens tight junctions
- gluten enters blood stream and promotes auto-immune response which degrades gut epithelial barrier and exacerbates immune response by augmenting T-cell recruitment
Loss of epithelial structure: Hypermobility syndrome
- mutation in collagen genes disrupts epithelial adhesion to basement membrane, resulting in hyper-flexible joints and loss of cell polarity
- several forms
- mutations in COL1A1, COL1A2, COL3A1, COL5A1, COL5A2 and Tenascin
- poor attachment with laminin and collagen
