Cell Adhesion Flashcards
Adhesion of cells to each other and their extracellular matrix provides many of the cues neccessary for controlling:
- Cell migration
- Cell shape
- Survival
- Proliferation
- Differentiation
These events regulate an organism’s normal development, maintenance, and recovery from injury and infection.
Defects in the pathways associated with cell adhesion provide the basis for:
- Cell transformation
- Cancer cell metastasis
- Developmental defects
- Cardiovascular disease
Protein complexes forming at specific sites of cell membranes (typically epithelium)
cellular junctions
cellular junctions organize contacts of cells with one another through:
- Adhesion
- Definition of cellular domains
- Control of permeability of epithelium
- Intracellular signaling
- Intercellular communication / signal transmission
Cellular junctions organize contact between cells and extracellular matrix:
- Anchoring
- Intracellular signaling
Typical components (cellular junctions)
- Transmembrane adhesive protein
- Cytoplasmic adapter (anchor) protein
- Cytoskeletal filament
Arrangement (cellular junctions)
- Macula: patch-like junction of limited extent
- Zonula: junction which encircles the entire cell
Junctional combinations
- Junctional complex (terminal bar): cuboidal or columnar epithelium
- Intercalated disc: cardiac muscle
Typical three-component arrangement
Types of junctions
- Gap (Nexus) junction (communicating junction)
- Tight junction (occluding junction, zonula occludens)
- Adherens junctions
- Cells attaching to other cells
- Adherens junction (or zonula adherens, intermediate junction)
- Desmosome (macula adherens)
- Cells attaching to / anchoring in the extracellular matrix
- Hemidesmosome
- Focal adhesion
- Cells attaching to other cells
Three (Four) functional classes of cell junctions in animal tissues
- Anchoring junctions
- Adherens Junctions
- Occluding Junctions
- Tight Junctions
- Channel-forming Junctions
- Gap Junctions
- Signal-relaying junctions
Summary figure of cell adhesion proteins
Gap/Nexus/Communicating junction
- Plaque-like junction
- Cell membranes of neighboring cells very close together; intercellular space only 2-3 nm
- Can be found in all basic tissue types
- Common in epithelial cells, smooth and cardiac muscle cells, neuronal cells, and osteocytes
Integral membrane protein
connexin
6 connexins form connexon (connexin hemichannel)
Connexon has central channel (diameter 2nm)
Connexons of one cell connect to connexons in adjacent cell to form hydrophilic channel
Tens to hundreds of aligned connexon pairs hexagonally packed in gap junction
Aqueous channel formed between cytoplasm of adjacent cells
Passage of small signaling molecules and ions possible
Connected cells are electrically coupled for coordinated responses to stimuli
Different members of connexin family result in differences in permeability
Connexin mutations are linked to:
- deafness
- cataracts
- Charcot-Marie-Tooth demyelinating disease
- oculodentaldigital dysplasia
Tight/occluding junction
Anastomosing strands of adhesive transmembrane proteins
Linear series of contacts to proteins of adjacent cell
Intercellular space obliterated at contact site
Junction encircles entire cell
Found close to the apical end of cuboidal or columnar epithelial cells
Transmembrane proteins (tight/occluding junction):
- members of claudin family (4 pass membrane proteins)
- occludin
- junctional adhesive
Transmembrane adhesive proteins interact homotypically with proteins in adjacent cell
Some cytoplasmic proteins (tight/occluding junction):
- kinases
- transcription factors
- cell polarity-related proteins
Actin filaments associated
Tight/occluding junction:
Movement of ions and small molecules in intercellular space:
Tightness (permeability):
Movement of membrane proteins:
Movement of ions and small molecules in intercellular space prevented / controlled
Tightness (permeability) depends on number of junctional strands, their completeness, and type of adhesive protein
Movement of membrane proteins limited
Adherens junctions
Cells held together or attached to/anchored in the:
Intercellular space between attached cells:
Adhesive junctions commonly involved in:
Loss of contact to adjacent cells or extracellular matrix may trigger:
Cells held together or attached to / anchored in the extracellular matrix
Intercellular space between attached cells: 20 nm wide at location of adhesive junction
Adhesive junctions commonly involved in (intra) cellular signaling (e.g. for nuclear transcription, tumor suppression, differentiation)
Loss of contact to adjacent cells or extracellular matrix may trigger apoptosis or result in loss of polarity
Cell-to-cell adhesive junctions:
Cell-to-ECM adhesive junctions:
- Cell-to-cell adhesive junctions:
- Transmembrane adhesive proteins members of cadherin (calcium ion-dependent proteins) family
- Cytoplasmic adapter proteins members of the catenin family
- Cell-to-ECM adhesive junctions:
- Similar to cell-to-cell adhesive junctions, but:
- Transmembrane proteins members of integrin family (heterodimers with alpha and beta subunits)
Adhesive junction with electron-lucent intercellular space and ___________on cytoplasmic face
Associated with ____________
Adhesive junction with electron-lucent intercellular space and ‘fuzzy’ plaque on cytoplasmic face
Associated with belt-like band of actin
Encircles entire cell (zonula)
Found basal to tight junction zonula in epithelial cells
- Transmembrane adhesive proteins (Adherens junction):
- Cytoplasmic adapter proteins:
- Interact with:
- Cytoskeletal element:
- Transmembrane adhesive proteins: E-cadherin; (nectin)
- Cytoplasmic adapter proteins: a- and b-catenin; (p120 catenin, afadin, vinculin, a-actinin)
- Catenins interact with cytoplasmic domain of trans-membrane protein, cytoskeletal proteins, and other cytoplasmic proteins
- Cytoskeletal element: actin filaments (continuous with apical terminal web)
Adheren junction functions:
- Contribution to adhesive force between one cell and another
- Support to apical domain of epithelial cell
- Intracellular signaling
Desmosome
- Disk-shaped adhesive junction (macula)
- Electron-dense cytoplasmic attachment plaque
- Intercellular space (ca. 30 nm; somewhat wider than in ZA) filled with highly-ordered proteins
- Found basal to zonula adherens in epithelial cells in band encircling cell as well as scattered over lateral cell surface
- Common in many tissue types
Transmembrane adhesive proteins (cadherins) - Desmosome:
Cytoplasmic adapter proteins (catenin):
Cytoskeletal element:
- Transmembrane adhesive proteins (cadherins): desmoglein, desmocollin
- Interaction of cadherins from adjacent cells results in electron-dense line in intercellular space
- Cytoplasmic adapter proteins (catenin): desmoplakin, plakoglobin, plakophilin
- Cytoskeletal element: intermediate filaments (anchoring in catenin plaque); type depends on tissue type
Autoimmunity to Desmosomes (Cadherins)
Pemphigus Vulgaris
Intra-oral view showing several lesions occurring predominantly on the buccal gingiva and appearing as small white pustules and a few ulcerated areas associated with gingival growth. 1B) Full mucosal healing after high-dose systemic corticosteroid treatment. 1C) Histopathological sections revealing well-defined foci of suprabasal acantholysis with crusting and a few neutrophils in the overlying space with mixed lymphocytes and eosinophils. 1D) Direct immunofluorescence showing bright intercellular deposition of IgG and C3 in the epidermis.
Linked to mutations in Desmosome Proteins
Epidermolysis Bullosa
Junctional Combinations
- Epithelial Junctional complex
Symmetrical structures formed between adjacent cells and consist of three components:
- a band of tight junctions (TJ), forming an occluding zone in the top position
- a band of anchoring junctions in the middle position (zonula adherens, ZA)
- a circle of spot desmosomes (DES) in the bottom position (macula adherens)
Junctional combinations
Intercalated disc:
*
Junctional combinations
Intercalated disc:
- Fascia adherens
- desmosomes
- gap junctions
Adhesion to basement membrane (basal lamina):
- Sheet-like arrangement of extracellular matrix proteins ( ca. 20-100 nm wide)
- Binds epithelium to underlying connective tissue
- Also found around muscle cells and nerve fibers
- Provides metabolic support
- Filters material (barrier function)
- Controls epithelial growth and differentiation; prevents downward epithelial growth
Basement membrane (Basal lamina)
Components:
Layers (visible only in TEM):
- Components:
- Heparan sulfate (glycosamino-glycan)
- Collagen type IV
- Fibronectin
- Laminin
- Entactin
- Collagen type III
- Collagen type VII (anchoring fibrils)
- Layers (visible only in TEM):
- Lamina lucida
- Lamina densa
- Lamina fibroreticularis
Hemidesmosome
- Provides tight anchoring of epithelial cell to basal lamina and underlying connective tissue
- Plaque-like adhesive junction morphologically similar to a half-desmosome
- Forms at the basal side of certain epithelial cells in zone of contact with basal lamina
- Transmembrane adhesive proteins (hemidesmosome):
- Binds to:
- Cytoplasmic adapter proteins:
- form:
- Cytoskeletal elements:
- Transmembrane adhesive proteins: integrin (a6b4)
- Integrins bind to basal lamina glycoprotein laminin
- Cytoplasmic adapter proteins: bulbous pemphigoid antigen 230 (BP230); plectin
- Cytoplasmic proteins form dense plaque
- Cytoskeletal element: intermediate filaments (anchoring in plaque)
Focal adhesion
- Dynamic assembly of many (>50) different proteins
- Provides linkage of cell to extracellular matrix
- Important for intracellular signaling
- Transmembrane adhesive protein: integrin heterodimers
- Cytoplasmic adapter proteins: a-actinin, vinculin, talin
- Cytoskeletal element: actin filaments
- Integrins bind to ECM proteins fibronectin, laminin, collagen
Summary Figure
Summary Table
