Cell Junctions and Adhesions Flashcards
Briefly describe the different types of cell junctions
1) Occluding/Tight Junctions
2) Mechanical/Adherens Junctions
a) Site of attack for actin
- Intercellular junctions: belt-like junctions - zonula adherens
- Cell-matrix junctions: focal adhesions
b) Site of attack for intermediate filaments
- Intercellular junctions: desmosomes
- Cell-matrix junctions: hemidesmosomes
3) Communicating Junctions
- Gap Junctions
- Synapses
What are occluding/tight junctions?
- Function
- Description
- Protein composition
Functions:
1) Maintain cell polarity: by not allowing proteins located in the apical to move to the basolateral domain
2) Control permeability (paracellular pathway)
- Have a belt-like distribution at apical domain
- Seal the space between epithelial cells and regulate paracellular pathway
- Not-associated with cytoskeletal components
Proteins:
- Occludins and claudins are the molecular basis
> they bind in a homophilic manner
- Zonula occludens proteins (ZO1-3) represent the scaffold: facilitate the interaction of occludin, claudins and JAMs with F-actin
Describe the different types of Mechanical/Adherens Junctions
1) Zonula adherens/belt-desmosome
- anchorage junction with a belt-like distribution
- associated with actin filaments
- function: keeps cells together (cell-cell)
2) Macula adherens/spot desmosome
- anchorage junction with a spot-like distribution (cell-cell)
- associated with intermediate filaments
3) Hemidesmosome
- link basal domain of epithelial cell to basal lamina (cell-matrix)
- intermediate filaments are associated with a plaque
4) Focal adhesions
- cell-matrix adhesion associated with actin filaments
Describe communicating/gap junctions
Functionally connect two adjacent cells
Examples of functions:
- propagation of excitation in cardiac muscle, smooth muslce, central nervous system
- regulation of early phases of development
- diffusion of nutrients and signals in avascular tissues
- allow passage of molecules <2000 Daltons (small, not proteins)
Formed by connexons
- six connexins assemble to form 1 connexon
- two connexons form a hydrophilic channel
- heteromeric: different connexins within 1 connexon
- heterotypic: different connexins in both cells (a channel)
Junctions are stable but can be disrupted by intercellular conditions:
- Open: low Calcium & high pH
- Closed: high Calcium & low pH
Talk about Desmosomes (belt-desmosome and spot desmosome)
For both:
- Cytoplasmic dense plaque proteins: desmoplakin, plakoglobin and plakophilin
- Desmosomal CADHERIN (connection): desmoglein & desmocolin
> homophilic (mainly) and heterophilic interactions
- Cadherins bind to CATENINS
- Development: appears at 32-cells stage
Junctions are stable but can be disrupted to allow cell movement or division:
> low Calcium > reduces desmosomes as cadherins require Ca
> tyrosine phosphorylation > increases desmosomes
-BELT DESMOSOME (Zonula Adherens)
Function: keep cells together through actin cytoskeleton
SPOT DESMOSOME (Macula Adherens)
- spot adhesions through intermediate filaments
Type of intermediate filament depends on the tissue:
- keratin: epithelial cells
- desmin: myocardial cells
- vimentin: meningeal cells and dendritic cells of lymph nodes
Talk about the two Cell-Matrix Adhesions:
HEMIDESMOSOMES
- Anchorage between cell and basal laminar
- Intermediate filament involvement
- Other proteins involved: BPAG1&2, plectin and integrin subunit B4 (INTEGRINS), anchoring filament (laminin 5), plaque (similar to spot desmosomes)
FOCAL ADHESIONS
- Anchorage between cell and basal laminar
- Similar to hemidesmosomes but with actin filaments and also involves INTEGRINS
What are the different types of Transient Adhesion Molecules?
CALCIUM DEPENDENT
1) Cadherins (homophilic interactions)
2) Selectin: binds mainly to carbohydrates on surface of opposite cell
CALCIUM INDEPENDENT
1) Immunoglobulin superfamily: bind mainly integrins with homophilic interaction
2) Integrins: bind to nectins or to proteins of Ig superfamily
Talk in detail about Cadherins as transient adhesions
- 4 different extracellular domains which require calcium to maintain their structure
- Form homophilic interactions with other cadherins of same type
> E-cadherins: epithelia
> N-cadherins: nervous and muscular cells
> P-cadherins: placental cells and in epidermis
Importance of Catenin Interaction > regulates cell proliferation
- Beta catenins can only bind to cadherins when cells are close together
- When there’s no room for proliferation cadherins from opposite cells interact > interact with beta catenins > inhibit proliferation
- When there is space between cells (junctions not formed), beta catenin is not bound to cadherins > B-catenin travels to nucleus > promotes cell proliferation
APC Complex:
For degradation of B-catenin when a junction is made so there is not an excess of beta catenin in cytoplasm
- If Abnormal APC Pathway > no degradation of B-catenin > colorectal tumours
What are selectins?
- Make intercellular adhesions (not junctions)
- Calcium dependent domains > maintain structure
- Heterophilic interactions
- Binds carbohydrates
- Key for extravasation of WBC\
- L-, E-, P-selectins
Talk about the Immunoglobulin (Ig) Superfamily adhesives?
They are CAMs (cell adhesion molecules)
- Folded into 2-6 immunoglobulin-like domains
- Homophilic binding
- Calcium independent
- ICAM (intercellular) and VCAM (vascular) play important role in T cell interactions, and binding of leukocytes to activated/resting endothelial cells
What are the properties of Integrins?
- Ca independent
- Two subunits: alpha and beta
- Heterophilic binding: bind nectin or Ig superfamily
- In intracellular portion, binds to cytoskeleton and is responsible for anti-apoptotic signalling > adhesion to other cells or to ECM prevents death of the cell
Describe the Basement/Basal Membrane (composition, functions, location, production)
Is an a-cellular structure defined by two layers/laminae:
1) Basal lamina: laminin, type IV collagen, glycosaminoglycans
2) Reticular lamina: Type III collagen (aka reticular fibres)
Functions:
1) Molecular filter
2) Selective cell barrier in nervous tissue > allows separation of compartments, - - 3) Tissue regeneration and differentiation (works as a niche)
4) Mechanical Support
Location: Epithelial, muscle, adipose, Schwann Cells
Production:
- produced by both epithelial and underlying connective tissues
Talk more about the molecules which compose the basal lamina (laminin and type IV collagen)
Laminin: (a type of nectin)
- cross-shaped molecule which is the connecting protein of the entire basal lamina complex
- organises network of proteins and binds to different components of the basal lamina (collagen, proteoglycans, integrins)
(Type IV) Collagen Production:
1) pro-collagen molecules secreted as short fragments
> can’t self-assemble as peptides at end of molecules
2) Cleavage of peptides allows self-assembly ONLY in ECM (as no cleavage enzyme inside cell)
NB: Type IV collagen doesn’t have peptides > only organised in networks (not tight fibres)
> very resistant to forces acting perpendicularly > gives structural integrity
Describe the different Surface Specialisations of the Apical Membrane
Microvilli:
