Structure of Epithelia Flashcards
What are the fundamental similarities in physiology between the kidney, gut and lung?
Systemic BP CO2 balance and excretion Acid-base Balance O2 sensing Fluid Secretion Fluid Absorption
What are the general characteristics of the epithelium?
Cells are packed into sheets
Cells form apical and basolateral domains which are oriented the same way throughout
Cells attach to a thin, fibrous basement membrane
Epithelia line surfaces of cavities and structures throughout the body - also form glands
Sheets lack blood vessels but contain nerves
How are the organs of the body formed in development?
Epithelia act in conjunction with mesenchyme
How might epithelia be classified?
Cell shape - cuboidal, columnar, squamous
Organisation in sheet - single, stratified, pseudo-stratified
Specialised forms - ciliated, neuronal connections, mucus secretion
Name the types of epithelium in the alveolus
AV type 1 - sqaumous - surface area for gas exchange
AV type 2 - cuboidal - fluid secretion, surfactant secretion, stem cell for AV type 1
Endothelium - squamous - gas exchange, capillary wall
Where are neuroepithelial bodies in the lung and what is their function?
At the junction of the upper airways. Have chemosensing function regulating O2 in the airway and breathing rate
What is the function of the epithelium in the Kidney nephron and collecting duct?
Ion transport
Fluid Homeostasis
Hormone Secretion
Acid- base Balance
What is the type and function of the epithelium in the Gut villus?
Simple, columnar with goblet cells.
Ion transport, fluid homeostasis, mucus and digestive enzyme secretion, nutrient absorption
Why is polarity crucial for function?
Gives direction to the transport of ions
Specialisation of function at one end of cell or the other
Supports formation of complex architectural shapes
How might loss of polarity lead to lung disease?
Flu -> disorganised ion transport -> oedema
How might loss of polarity lead to cancer?
cell detachment -> metastasis -> reorganisation as tumour
What is the adherens junction?
cell-cell recognition site where primitive contacts are made through homophillic E cadherin interactions.
What makes up the Adherens Junction?
E-cadherin
a, b, y, p120 catenins
F-actin
What is essential for E-cadherin homodimerisation and how many binding sites are there for this?
4 binding sites for Ca2+
Where are the catenins found?
on the COOH carboxy terminus of E-cadherin
What is the function of p120?
Interacts with cell membrane and E-cadherin to regulate cell junction type
What is the function of a-catenin?
Forms a homodimer that anchors actin filaments to the membrane and pulls cells together in shape
What is the function of b-catenin?
Released from E-cadherin by proteolysis in the absence of homodimerisation or degradation and acts as a nuclear signal to stimulate loss of polarity and cell growth
What is y-catenin also known as?
plakoglobin
What is the function of y-catenin?
alters the cell junction type and is common to desmosomes
What is the function of F-actin?
forms supporting belt structure around inner cell membrane and supports transition into cuboidal structure and recruits other cytoskeletal elements i.e. tubulin
Where do tight junctions form?
Apical side of the Adherens Junction
What is the tight junction?
Creates an impermeable barrier that blocks paracellular movement of molecules between cells and acts as a fence between apical and basolateral membranes
What is the basic unit of a tight junction?
the occludin
What are the zona occuldens?
proteins that anchor cytoskeletal proteins actin and tubulin to the tight junction complex
What sort of structures might tight junctions support?
microvilli, cilia
Give an example of how tight junction permeability is regulated?
Glucose Transport
SGLT1 stimulates NHE3
Rise in NHE3 activity increases H+ extrusion and alkalinises the cytoplasm
Alkalinisation activates MLCK causing actin ring contraction and TJ opening
Paracellular nutrient uptake rate increases as transepithelial resistance falls
How are the apical and basolateral membranes distinguished by the tight junction?
Par3 recruits PTEN to the tight junction which enriches PIP2 to the apical membrane
PI3K localises to the adherens junction which enriches PIP3 in the basolateral membrane
What is the function of desmosomes?
to form loose junctions between cells enabling cell shape to distort without tearing due to mechanical strain
Where are desmosomes most common?
in cells exposed to stretch (lung) and shear (vasculature)
What are the key proteins of the desmosome?
desmoglein and desmocollin
What are the proteins which anchor desmoglein and desmocollin?
plakoglobin and plakophillin heterodimers
What does desmoplakin bind?
desmin, the cytoskeletal protein to the desmosome complex
What is the gap junction formed from?
hexamers of connexin proteins
What is the function of the gap junction?
function as channels that connect the cytoplasms of two cells and establish Planar Cell Polarity
How are the connexin hemi-channels connected?
EC connexin loops
What is the basement membrane essential for?
cell metabolism, survival, proliferation, migration
What is the basement membrane?
ECM underlying all epithelia connecting cells to connective tissue and providing structural support
What are the major components of the basement membrane?
Laminin - primary organiser of BM proteins
Integrins - expressed on basolateral side of cell. bind to laminin
Collagens and Fibronectin - chicken-wire-like meshwork that gives BM its tensile strength
Nidogen and Perlecan - link laminin to collagen and fibronectin
What forms the lamina lucida?
Integrins
What forms the lamina densa?
Laminin
What connects laminin to collagen and fibronectin?
nidogen and perlecan
What cellular process might lead to cancer in epithelia?
degradation of E-Cadherin releasing b-catenin which enters nucleus and increases cell growth by activating LEF-1/TCF driven expression of cell cycle genes
How does gluten activate an autoimmune response?
gluten stimulates zonulin secretion from gut epithlium which opens TJ
gluten enters blood stream and promotes immune response which degrades gut epithlial barrier and exacerabates T cell recruitment
What is hypermobility syndrome?
mutation in the collagen gene disrupts epithelial adhesion to the basement membrane resulting in hyperflexible joints and polarity loss esp. in the lung
