Epithelial Cell Domains
Charles L. Hitchcock, MD, PhD
Department of Pathology
Primary Learning Objective
• Compare and contrast the normal
morphologic features of epithelial tissue with
the specific morphologic changes associated
with disease.
Secondary Learning Objectives
• Identify the morphologic features of the apical
domains of epithelial cells from an image or
description.
• Compare and contrast the location and molecules
making up the junctional complexes in the lateral
domains of epithelial cells from an image or
description.
• Describe the structure and functions of the
molecules involvement in epithelial cell-basement
membrane binding.
Cellular Domains
Objective 1
• Identify the morphologic features of the
apical domains of epithelial cells from an
image or description.
Apical Domain
• Surface:
• Enzymes, ion channels, and carrier proteins
• Specialized structures
• Microvilli
• Cilia – motile and non-motile
• Stereocilia
Microvilli
• Finger-like extensions of
•
•
•
•
the plasma membrane of
apical epithelial cell.
“Brush boarder” – renal
tubules
“Striated border” –
intestines
Their core contains crosslinked actin filaments.
Movement due to
terminal web contraction.
Microvilli
Microvilli
Structure
Microvilli Movement
Motile Cilia
Ciliated Respiratory Epithelium
GC
GC
GC
GC
Loose Connective Tissue
c
Microtubule
Primary Cilia Dyskinesia
(Kartagener Syndrome)
• Rare autosomal recessive
• Reduction in dynein arms; lack
central tubules; 8-1 doublet
pattern, etc. leads to an
uncoordinated beating of the
cilia.
• Chronic bronchitis and
sinusitis, pneumonia, otitis
media, hearing loss, male
infertility due to an immotile
cilia on sperm. Situs inversus,
Primary Cilia
Summary – Apical Domain
• Surface enzymes, ion channels, and carrier proteins
• Microvilli – increase area for absorption – intestine and renal
tubules
• Motile cilia – respiratory epithelium
– 9-2 configuration of microtubule doublets
– A and B microtubules with two dynein arms forming cross-bridges from
the A microtubule to an adjacent B microtubule
– Primary Cilia Dyskinesia –loss of dynein bridges – situs inversus,
sinusitis, immotile sperm, URI and LRI
• Non-motile cilia –in kidneys respond to fluid flow as a
mechanoreceptors and calcium ion channels – gene mutations
lead to cyst formation
Objective 2
Compare and contrast the location and molecules
making up the junctional complexes in the lateral
domains of epithelial cells from an image or
description.
Epithelial Cell Lateral Domains
Zonula Occludens - (Tight Junctions)
Zonula Adherens
Macula Adherens (Desmosome)
Keratin
filaments
Dense
plaque Desmoplakin
Plakoglobin
Cadherins desmoglein
desmocollin
Gap Junctions
(Communicating Junctions)
Connexon 6 connexin
proteins
Ca+2
cAMP
Summary – Lateral Domain
Junctional Complexes
• Zonula occludens - apical, belt-like continuous barrier,
occuldin and claudins are critical proteins
• Zonula adherens – belt-like structure, link cytoplasmic actin
network via E-cadherins attached to alpha-actinin and
vinculin plaque just below the plasma membrane
• Macula adherens - “spot welds”, desmoglein and desmocollin
homodimers that link cytoplasmic keratin intermediate
filaments networks of adjacent cells via desmoplakin and
plakoglobin containing dense plaques.
• Gap junctions - connexin containing pores that provide rapid
intercellular movement of ions and small signalling
molecules.
Cell Adhesion Molecules
• Transmembrane proteins
• Separate extracellular
cytoplasmic and binding
domains
• Extracellular binding domain
can be calcium dependent or
independent
• Link cytoskeletal systems
between cells
• Involved in signal transduction
Cadherins
• Transmembrane
homodimers
• Links to actin or
intermediate filaments
• calcium dependent
binding,
• Altered in tumor
progression
Selectins
• Binds to specific
carbohydrate on surface
glycoproteins and
glycolipids
• Binding is calcium
dependent
• Cytoplasmic tail in linked
to actin cytoskeleton
• Functions in leukocyte
homing
Immunoglobulin Superfamily
• Immunoglobulin-like molecules
• Homophilic and heterophilic
binding that is calcium
independent (..CAMs and CD
designations)
• Leukocyte adhesion, neurite
growth, and myelination
• CD4 is the receptor of HIV
Integrins
• Heterodimeric transmembrane
proteins
• Cell-cell and cell-ECM calcium
independent binding
• Facilitate cell movement in the
ECM and two-way signalling
• In hemidesmosomes,
Summary – Lateral Domain
Cell Adhesion Molecules
• Cadherins – homodimeric proteins, calcium dependent
homophilic binding, linking actin or cytoskeletal filament
networks of adjacent cells
• Selectins – heterophilic binding to specific carbohydrates on cell
surface glycoproteins and glycolipids, links to actin filament
network, leukocyte homing and transmigration
• Immunoglobulin superfamily – Homophilic binding and
heterophilic binding to integrins, leukocyte binding
• Integrins – heterodimeric transmembrane, proteins, heterophilic
binding of ECM adhesive proteins, to linked to actin cytoskeleton,
signal proteins, hemidesmosomes, and cell motility.
Objective 3
• Describe the structure and functions of the molecules
involvement in epithelial cell-basement membrane
binding.
PAS Stain Renal Tubules
Basement
Membrane
Basal Lamina
Reticular
Lamina
Electron Micrograph of the Basement Membrane
collagen fibers
Basal Lamina Components
• 3D lattice of extracellular
matrix components
• Collagens – Type IV
predominates, Type VII
anchoring fibrils attach to
hemidesmosomes.
• Multiadhesive proteins –
laminin 5, fibronectin, entactin
• Proteoglycans – most of the
basal lamina volume
Hemidesmosome
Focal Adhesions
Clinical Relevance
Pemphigus vulgaris
IgG to desmoglein 3
Pemphigus folaceous
IgG to desmoglein-1
Clinical Relevance
• Mutations of hemidesmosomal proteins
associated with epidermolysis bullosa (EB)
variants
– COL7A1 - dystrophic EB- severe blistering apparent
from birth – with loss of tethering of basement
membrane to dermal matrix
– Cytokeratins filaments – epidermolytic EB
– Laminin and integrins – junctional EB
• Autoantbodies to hemidesmosomal
proteins gives rise to bullous pemphigoid
– IgG to BP180 and BP230 proteins
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