structure and organisation of epithelium Flashcards
what is epithelia
tissue which interfaces with the external environment
examples of epithelial tissue
gut, ear, skin, nasal
how are cells in epithelia organised
packed into sheets
what domains do epithelial cells form
apical and basolateral domains which are polarised (orientated) the same way throughout the epithelial sheet
how do epithelial cells sit
next to each other
what are epithelial cells attached to
a thin, fibrous basement membrane
what does epithelia line
the surfaces of cavities and structures throughout the body
what can epithelia form
glands
what do epithelial sheets lack
blood vessels (but they can still interact with nearby vessels)
what do epithelial nerves allow neural contribution to
sensation, absorption, protection and secretion
what do epithelial cells do within development
act in conjunction with mesenchyme to form nearly every organ in the body
what does epithelia contribute to
embryonic development and to the maintenence and function of the body throughout its life
what is epithelium classified by
its morphology
what are the cell types of epithelia
cuboidal, columnar, squamous
how can epithelial cells be organised
simple epithelium (single layer), stratified epithelium (several layers), or pseudo-stratified epithelium (one layer, cells of varying heights)
what are the specialised forms of epithelium
ciliated (primary cilia, motile cilia), neural connections (neuroepithelial cells) and mucus secreting (goblet cells)
what are the epithelias main functions
fluid secretion, mucus secretion, motile cilia and pathogen defence
what do alveolar type-1 cells (squamous) do
surface area for gas exchange
what do capillary endothelium cells do (squamous)
capillary wall and surface area for gas exchange
what do type-2 alveolar cells (cuboidal) do
fluid secretion (airway surface liquid), surfactant secretion (mechanical support) and stem cell for AT-I cells
innervated epithelium functions
(lung neuroepithelial bodies)
functions: chemosensing and regulation of breathing
cuboidal secretory epithelium functions
(kidney nephron and collecting duct)
functions: ion transport, fluid homeostasis, hormone secretion (renin; erythropoietin) and acid/base balance
simple columnar epithelium with goblet cells functions
(gut mucosa)
functions: ion transport, fluid homeostasis, mucus and digestive enzyme secretion and nutrient absorption
endothelial interaction with astrocytes functions
(BBB)
functions: ion transport, fluid homeostasis and selective hormone signalling
ciliated neuroepithelual “hair” cells functions
(innervated sensory epithelium of the ear)
functions: mechanosensing and neurotransduction
neuroepithelium with highly modified cilium
(retinal photoreceptors of the eye)
functions: photoreception and neurotransduction
what is polarity crucial for
function
what is polarities main functions
gives direction to the transport of ions and nutrients (vectored transport)
specialisation of function at one end of the cell or the other (retinal/hair cells)
supports formation of complex architectural shapes (branching morphogenesis)
what is loss of polarity key for
disease
how does respiratory failure occur
influenza virus infection, disorganised ion transport, oedema of the lung
how does cancer occur
cell detachment and movement (metastasis), re-organisation as a tumour
what is the organisation of epithelial cell junctions in an organised sheet
hemidesmosome junction - gap junction - desmosome junction - adherens junction - tight junction - microvilli
what is the function of microvilli
increase surface area for interactions with the environment
what do the adherens junctions do
establish apical-basolateral polarity
what is cell-to-cell recognition
primitive contacts made through homophilic epithelial (E) cadherin interaction
F-actin bundles are diffuse
the adherens junction (zona adherens) binds the cells together
where do E-Cadherins extend from
external surface of the cell
what does the homophilic binding domain within the adherens junction mean
it recognises and binds to itself
what are cadherins
cell adhesion proteins
what holds the cells in contact
Ca2+ dependant homodimerisation between extracellular domains
what is the anchor for p120, a, b and g Catenin
Carboxy-terminus
what is p120
a prototypical catenin isoform
what does p120 do
it stabilises adherens junction and initiates formation of other junction complexes
what does a-Catenin form
a homodimer that anchors actin filaments to the membrane
where is b-Catenin released from and what does it do
E-cadherin by proteolysis
acts as a nuclear signal to stimulate loss of polarity and cell growth
what does g-Catenin (plakogolin) do
alters types of junction complex and is common to desmosomes
what do adherens junctions do
anchor F-Actin (which forms supporting belt sturcture around inner cell membrane)
supports transition to cuboidal structure and recruits other cytoskeletal elements (eg tubulin)
where is b-Catenin anchored to
the cytoskeleton
what is the dual role of b-Catenin
sequestered at adherens junction - cell growth neutralised; polarisation can begin - when its ‘free’ it acts as a transcription factor
what happens if adherens junction is disrupted
b-Catenin moves to the nucleus and promotes cell growth and loss of polarity - this is a metastasis cue
main mode of action of junctions!!!
junction complexes stabilise cell structure and inhibit cell cycle passage by sequestering key transcription factors
where do tight junctions form
on the apical side of the adherens junction
what do tight junctions do
create an impermeable barrier that blocks paracellular movement of molecules between cells which acts as a fence to separate the apical and basolateral membranes (barrier and fence function)
what is the basic unit of tight junctions
occludin
what does homodimerisation of occludin extra-cellular domains do
forms an impermeable seal between cells
what do transmembrane occludin domains do
seperate apical and basolateral membranes - prevents movement of proteins between these membranes
how do tight junction complexes work
they run as a belt around cells, sealing apical and basolateral membrane domains and the join between cells
what proteins anchor cytoskeletal proteins (actin / tubulin) to the tight junction complex
zona occludens (ZO-1,2&3)
what do tight junctions anchor the cytoskeleton for
apical membrane structures (microvilli, cilia)
what are microvilli supported by
actin anchored to actin ring
tight junctions activate what type of uptake
paracellular
what regulates phosphoinositide (Ptdlns) content of the apical and basolateral membranes
phosphoinositide-3-kinase (PI3K) and its inhibitor (PTEN)
what acts as a recognition signature for protein transport to either membrane
Ptdlns
what recruits PTEN to tight junctions
Par3
what does PTEN enrich
PIP2 in apical membrane
what does PI3K localise to
adherens junction
what does PI3K enrich
PIP3 in basolateral membrane
what do desmosomes form
loose junctions between cells
what do desmosomes enable
cell shape to distort without tearing during mechanical strain
where are desmosomes most common
in cells exposed to stretch (lower airway of lung) and shear (vascular tissue; kidney glomerulus)
what are desmosomal junctions composed of
cadherin-family proetins known as desmoglein, desmocollin which are anchored in the membrane by plakoglobin and plakophilin heterodimers
what does desmoplakin bind desmin (a cytoskeletal protein) to
the desmosome junction complex
what do gap junctions do
connect epithelial cells as a syncitium
what are gap junctions formed from
hexamers of connexin proteins
what do gap junctions function as
channels that connect the cytoplasm of one cell to another
what do gap junctions establish
lateral or planar cell polarity (PCP)
how many connexins form a hemi channel
6
what links hemi channels between neighbouring cells
extracellular connexin loops
what do channel pores facilitate
electric and metabolic coupling between cells
what is the bystander effect
death of one cell spreads as a signal to neighbours
limits spread of infection by creating zone of cell death
what is another name for the basement membrane
the hemidesmosome
what is the hemidesmosome
an extracellular matrix underlying all epithelia connecting cells to connective tissue and providing structural support
what does the hemidesmosome do
link basolateral cells to collagen/fibronectin below - if unlinked, they become motile , and so cancerous
what is effected by basement membrane composition
cell metabolism, survival, proliferation and migration
what are the major components of the basolateral membrane
laminin, integrins, collagens & fibronectin and nidogen & perlecan
what does laminin do
primary organiser of BM proteins - forms lamina densa
what does integrins do
expressed on basolateral side of cell and from lamina lucida - bind to laminin
what does collagens and fibronectin do
chicken-wire-like meshwork that gives BM tensile strength
what does nidogen and perlecan do
link laminin to collagen and fibronectin
how does cell attachment between basolateral and basement membranes occur
through integrins
what occurs when a laminin mutates
brutal detachment
what are the common diseases that are caused by loss of epithelial structure
cancer, gluten intolerance, chron’s disease and hypermotility syndrome (EDS)
how does cancer occur
factors that cause loss of cell polarity disrupt cell junctions and promote cell growth and migration - loss of the tight junction fence
how does gluten intolerance and chron’s disease occur
activation of an auto-immune response which disrupts tight junction barrier function enhancing pathological paracellular transport
(basically allows allergens to cross barriers)
