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Human Epithelial Biology > Structure of Epithelia > Flashcards

Structure of Epithelia Flashcards

1
Q

What is a common quality of epithelial cells

A

they interface with external environment

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2
Q

Characteristics of epithelial cells

A
  • 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
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3
Q

What is an epithelia

A
  • 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
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4
Q

Shapes of epithelial cells

A
  • cuboidal (cube)
  • columnar (rectangular)
  • squamous (flat (e.g. skin))
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5
Q

Layers of epithelial cells

A
  • simple epithelium (single layer)
  • stratified epithelium (several layers)
  • pseudo-stratified epithelium (one layer, varied heights (e.g. in lungs))
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6
Q

Specialised forms of epithelial cells

A
  • ciliated (primary cilia, motile cilia)
  • neural connections (neuroepithelial cells)
  • mucus-secreting (goblet cells)
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7
Q

Example of squamous epithelial cell in lung alveolus

A

Alveolar type-I cells
- surface area for gas exchange

Capillary endothelium
- capillary wall
- surface area for gas exchange

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8
Q

Examples of cuboidal epithelial cells in lung alveolus

A

Alveolar type-II cells
- fluid secretion (airway surface liquid)
- surfactant secretion (mechanical support)
- stem cells for AT-I cells

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9
Q

Epithelial functions of lung bronchial airway

A
  • fluid secretion (airway surface liquid)
  • mucus secretion (particle clearance)
  • motile cilia
  • pathogen defence
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10
Q

Epithelial functions of lung neuroepithelial bodies (innervated epithelium)

A
  • chemosensing and regulation of breathing
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11
Q

Epithelial functions of kidney nephron and collecting duct (cuboidal secretory epithelium)

A
  • ion transport
  • fluid homeostasis
  • hormone secretion (renin, erythropoietin)
  • acid base balance
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12
Q

Epithelial functions of gut mucosa (simple columnar epithelium with goblet cells)

A
  • ion transport
  • fluid homeostasis
  • mucus and digestive enzyme secretion
  • nutrient absorption
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13
Q

Endothelial interactions in the blood-brain barrier

A
  • endothelial:astrocyte interactions
  • ion transport
  • fluid homeostasis
  • selective hormone signalling
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14
Q

Epithelial functions of innervated sensory epithelium of the ear (ciliated neuroepithelial “hair” cells)

A
  • mechanosensing
  • neuro transduction
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15
Q

Epithelial functions of retinal photoreceptors of the eye (neuroepithelium with highly modified cilium)

A
  • photoreception
  • neurotransduction
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16
Q

Why is polarity crucial for function

A
  • 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
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17
Q

Which order do epithelial cell junctions aquire apical-basolateral polarity

A

1) adherens junction
2) tight junction
3) desmosome junction
4) gap junction
5) hemidesmosome junction

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18
Q

Which order do epithelial cell junctions appear anatomically

A

1) tight junction
2) adherens junction
3) desmosome junction
4) gap junction
5) hemidesmosome junction

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19
Q

The adherens junction

A
  • responsible for cell-cell recognition
  • primitive contacts made through homophilic Epithelial Cadherin Interaction
  • F-Actin bundles are diffused
  • binds cells together
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20
Q

What are cadherins

A
  • 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
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21
Q

p120 Catenin

A
  • prototypical isoform
  • stabilises adherens junction
  • initiates formation of other junction complexes
22
Q

alpha-Catenin

A
  • forms homodimer that anchors actin filaments to membrane
23
Q

beta-Catenin

A
  • 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)
24
Q

gamma-Catenin (Plakoglobin)

A
  • alters type of junction complex and is common to desmosomes
25
Q

What is role of Catenins

A
  • bind F-Actin and build cytoskeletal structures
26
Q

Function of adherens junction

A
  • 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)
27
Q

How do junction complexes stabilise cell structure

A
  • inhibiting cell passage by sequestering key transcription factors
  • beta-Catenin provides an example of this
28
Q

The tight junction

A
  • 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
29
Q

Basic unit of tight junction

A

Occludin

30
Q

Formation of barrier and fence

A
  • 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
31
Q

Function of zona occludens proteins

A

anchor cytoskeletal proteins to the tight junction complex

32
Q

Proteins involved in tight junctions

A
  • ZO-1
  • ZO-2
  • ZO-3
  • Actin
  • Myosin
33
Q

Role of Phosphoinositide-3-Kinase (PI3K) and PTEN

A
  • PTEN is PI3K inhibitor
  • regulate phosphoinositide (PtdIns) content of apical and basolateral membranes
  • acts as recognition signature for protein transport to either membrane
34
Q

Role of Par3 in tight junction

A

recruits PTEN to tight junction

35
Q

Role of PTEN in tight junction

A

enriches PIP2 in apical membrane

36
Q

Role of PI3K in adherens junction

A

enriches PIP3 in basolateral membrane

37
Q

The desmosome

A
  • resist mechanical stretch and shear
  • form loose junctions between cells and enable cell shape to distort without tearing during mechanical strain
38
Q

Desmosomal junctions (macula adherens)

A
  • composed of cadherin-family proteins (desmoglein, desmocollin) which are anchored in the membrane by plakoglobin and plakophilin heterodimers
39
Q

Role of desmoplakin

A

binds desmin (cytoskeletal protein) to desmosome junction complex

40
Q

Consequences of weakened desmosomes

A
  • intraepithelial lesions within epithelial tissue
  • pemphigus vulgaris
41
Q

The gap junction

A
  • 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)
42
Q

Structure of the gap junction

A
  • 6 connexins form hemi channel
  • extracellular connexin loops link hemi channels between neighbouring cells
  • channel pore facilitates electric and metabolic coupling between cells
43
Q

Describe the bystander effect

A
  • 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’
44
Q

The basement membrane

A
  • provides structural support
  • extracellular matrix underlying all epithelia connecting cells to connective tissue
  • composition influences cell metabolism, survival, proliferation, migration
45
Q

Main components of the basement membrane

A
  • 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
46
Q

How does cell attachment between basolateral and basement membranes occur

A

through integrins

47
Q

Mutations in the hemidesmosome (basement membrane)

A

epidermolysis perlosia (affects ability of lamanin to bind to collagen)

48
Q

Loss of epithelial structure: cancer

A
  • 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
49
Q

Loss of epithelial structure: Gluten intolerance / Crohn’s disease

A
  • 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
50
Q

Loss of epithelial structure: Hypermobility syndrome

A
  • 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

Human Epithelial Biology (7 decks)

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