Epithelia

Gwen V. Childs, Ph.D.

Graduate Microanatomy

Common features of epithelia

• Cells are connected to one another providing a lining for a surface or a hollow organ or tube

• Sit on a layer of fine filaments, called a "basal lamina".

• Form a boundary between the external environment and the remainder of the organ.

• Control movement of substances into and out of that organ.

How are epithelia classified?

Depends on number of layers

One layer

Simple

Two or more layers

Stratified

Pseudostratified

Multilayered nuclei

Classification depends on shape

Flattened, scale-like

Squamous

Cells are cubes Cells are columns

Cuboidal Columnar

lumen

lumenlumen

Transitional Epithelium (Bladder)

Pseudostratified Columnar epithelium

Importance of cell shapeFlattened, squamous

cells

Reduced surface for passive transport

across cells

Can be stacked toprovide protective

layers

Taller, cuboidal or columnar cells

often expressstructural and

functional polarity

Apical surface functions

Basal/lateral surface functions

Absorption

secretion

Water and iontransport

Enzymeactions

receptivitysecretion

junctionsIon transport

communication

sensory

Importance of layering

Protect against friction and injury

Multilayered epithelia:

Lower layers regenerate upper layers

Barrier to water, diseasesome toxins, etc

Single layered epithelia:

Important in regulatedtransport of cells/molecules

Communication/gateway

Key cell structures at each surface

Microvilli, Cilia,Stereocilia

Specialized junctions

(Cellular interdigitations)Basal lamina + receptors

Increase surface area of cells 15-30X; Covered by glycocalyx; enzymes important in absorption are associated with this region

Core Actin filaments

Actin filamentsare held in bundlesby actin-bindingproteins: fimbrin, villin, or fascin

Actin filamentsare held at the tipof microvilli by amorphousanchoring proteins;capping preventsdepolymerization

Actin is boundto myosin along lateral walls

Terminal WebBase of

microvillus

Microvillus actin binds to more actin running horizontally.

Underneath the actin filaments are cytoskeletal filaments,also running horizontally

Terminal web actin is cross-linked byspectrin.

CiliaNine microtubuledoublets surrounda central pair

Doublets connectedby Dynein arms thatwalk along adjacent microtubule

Nexin spokes radiateinward, connectingthe doublets to the central pair

Specialized Microvilli

• Stereocilia are long microvilli

• Found in absorptive/secretory cells in epididymus (non-motile)

• Also found on special sensory cells in ear (cochlea)– Bending is a stimulus for sound or

position sensation.

Cilia/flagellar functions

• Move egg down fallopian tube

• Move Sperm

• Move mucous in respiratory tract.

• Olfactory epithelium– Bear receptors that bind chemicals– This receptor binding is the stimulus for

smell

SEM view of cilia and microvilli

Can you classify this tissue?

What kind(s) of junction(s) are in stratified squamous epithelium?

Anchoring junctions at thelateral surface

• Bind cells together via special ligands and their cytoskeletal systems – ligands are cadherins

• Junction differentiated by type of microfilament– Actin: adherent junctions– Intermediate filaments: desmosomes

Anchoring junctions : Desmosomes

• Like a spot weld or button.– Formed by a dense intracellular plaque on each

side into which keratin filaments are looped. (desmoplakins; plakoglobin; 75 kD polypeptide; desmoglein)

– Cadherin molecules (“calcium dependent adhesion molecules”) extend across the extracellular space to bind the cells together. (Desmocollins-I, II & desmogleins)

Desmosome

Two dense plaques:one on each cellmembrane

Cadherins connect the two plaques via homophilic binding

Cadherin bindingrequires Calcium

Intermediate filamentsloop into plaque

Adherent junctions

Two dense regionsone on each cellmembrane (alphaactinin)

Cadherins connect the two plaques via homophilic binding

Cadherin bindingrequires Calcium

Actin connects with dense regions on membrane

Pemphigus: skin disease

• Patients make antibodies against one of their desmosomal cadherans.

• Antibodies bind to desmosomal sites (only in skin and oral mucosa)

• disrupt connection between skin cells.

• Body fluid leaks into epithelial cells and causes blistering.

• Can be fatal if left untreated

Penphigus vulgaris

Penphigus Vulgaris

• Skin lesion histology:– Notice that the

separation occurs in that layer where the desmosomes are abundant.

Can you classify this epithelium?

Junctional complex

• Tight (occluding) junctions– Zonula occludens

• Zonula adherans (belt-like zone)• Desmosome

• Found frequently in columnar-type epithelia• Prevents entry between cells and helps to

maintain cell polarity

Microvilli

Occluding junction

Gap Junction

Specializations at the basal surface

• Basal/Lateral interdigitations

• Hemidesmosomes– Interactions between intermediate

filaments and basal lamina

• Focal contacts– Interactions between actin filaments

and basal lamina

Basal/Lateral Interdigitations

• Cells sit on multiple processes (like an octopus).

• These processes interdigitate with one another.

• Greatly increase surface area. • Process filled with mitochondria• On membrane are Na/K pumps (ATPase’s)

(important for active transport of sodium and water conservation)

Anchoring junctions: Hemidesmosomes

• Like a half desmosome at the base of the cells • links to basal lamina

– A plaque anchors intermediate filaments inside the cell--ends are buried in plaque (contains desmoplakin-like protein).

– anchoring proteins called “integrins”, bind from the keratin molecules inside to laminins in the basal lamina. (Integrins are receptors for specific extracellular matrix proteins). Bind like “velcro”

Anchoring junctions at thebasal surface

• Bind cells to extracellular matrix– ligands are integrins

• Junction differentiated by type of microfilament– Actin: focal contacts– Intermediate filament: hemidesmosome

Dense plaque (desmoplakin)

Cytoskeletal filaments(intermediate)anchored to plaque

Integrin molecules: Transmembrane receptorsfor extracellular matrix proteins (fibronectins,laminins, etc) found in basal lamina

fibronectin

Plasma membrane

Basallamina

Thickenedarea on membrane

Actin filamentsanchored to plaque

Integrin molecules: Transmembrane receptorsfor extracellular matrix proteins (laminins) found in basal lamina

laminin

Plasma membrane

Basallamina

What are integrins?• Extracellular matrix receptors in the cell membrane:

– Affinity relatively low (Ka= 106--109 liters/mole): Why would that help the cell?

– Depends on extracellular divalent cations (Ca++ or Mg++)

– binding activates signalling cascades

• Composed of two glycoprotein subunits: alpha and beta. Combination and types of subunits may dictate selectivity of binding.

How do integrins function, in general?• Regulated adhesion via integrins

controls route and movement of cells in the body.

• Could you apply this to wound healing?