cell junctions

Question 1

what are cell junctions

Answer 1

they are multi-protein complexes that link two neighboring cells, or a cell to the ECM within a tissue of a multicellular organism.

Question 2

cell junctions are abundant in

Answer 2

epithelial tissue

Question 3

What do cell junctions do ?

Answer 3

allow cells within a tissue to withstand external forces that try to pull them apart

Question 4

Classification of Cell Junctions:

Answer 4

By location:
• Cell – cell
• Cell – matrix

• By function:
• Anchoring
• Occluding
• Communicating (AKA channel-forming)

Question 5

Occluding junctions =

Answer 5

Tight junctions

Question 6

What are tight junctions ?

Answer 6

they are complex structures that seal the gap between adjacent epithelial cells

Question 7

tight junction’s location

Answer 7

apicolateral borders of adjacent epithelial cells

Question 8

Tight junction’s structure

Answer 8

They have a branching network of sealing strands that encircles the apical ends of epithelial cells

Each strand is composed of a long row of four- span transmembrane proteins:

1) Claudin
• The main structural component (backbone) of TJs
• Forms & regulates aqueous channels used for paracellular diffusion

2) Occludin
• Not essential for the assembly of TJs, but important for limiting junctional permeability

Question 9

how do the extracellular domains of claudins & occludins on neighboring cell membranes bind ?

Answer 9

homophilically, they act as a zipper to seal the intercellular space.

Question 10

what is localized in specific areas of TJs at tricellular contacts (corners where three epithelial cells meet) ?

Answer 10

the protein (tricellulin)

Question 11

What is the functions of tight junctions

Answer 11

1) Gates or selective permeability barriers that regulate paracellular transport of ions and small molecules.

• All TJs are impermeable to macromolecules, but their permeability to ions and small molecules varies between tissues.
• Targeting TJ proteins by pathogens increases the permeability of TJ, allowing the pathogens to invade the cell.

2) Fences that confine apical & basolateral lipids and proteins to their respective domains, thus play a role in polarity & transcellular transport of solutes.

• i.e., glucose transport across intestinal epithelial cells:
• Na+-driven glucose symports in the apical domain actively transport glucose from the lumen into the cell.
• Glucose uniporters in the basolateral domain passively transport glucose out & into the ECF.
• Na+ gradient is established & maintained by Na+/K+ pump
• Intercellular spaces are tightly sealed by TJs to prevent leakage of transported glucose back into the lumen.

Question 12

Communicating junctions =

Answer 12

Gap junctions

Question 13

What are gap junctions

Answer 13

It is an array of aqueous channels that interconnect the cytosols of adjacent cells:

• Allows ions & small hydrophilic molecules (< 1kDa) to pass by diffusion.
- i.e., amino acids, sugars, nucleotides, second messengers, metabolites.

• Excludes macromolecules.

Question 14

Where does gap junctions express ?

Answer 14

In most tissues (i.e., connective, epithelia, heart muscle & neurons).

Question 15

Gap Junction’s Structure

Answer 15

• Gap junction channel = 2 connexons (hemichannels)
• Single connexon = 6 connexins

Question 16

Gap Junction’s Functions

Answer 16

1) Electrical coupling of excitable cells:
• Rapid,simultaneous activation,hence synchronized contraction of heart muscle cells & smooth muscle cells of intestine, uterus & bladder.

2 ) Electrical synapses in the brain:
• Allow conduction of action potential at the synapse without the delay associated with neurotransmitter release.
• Allow for bidirectional signal transmission which increases neuronal sensitivity and promotes synchronous firing of a group of interconnected neurons.

3 ) Metabolic coupling of non-excitable cells:
• Coordination of non-excitable cells activities by bidirectional transport of ions, small metabolites & second messengers.

4 ) Provide a form of cell-cell adhesion. I

Question 17

what are the two anchoring junctions ?

Answer 17

1) Cell – Cell Anchoring Junctions:
• Link the cytoskeletons of two neighboring cells.
• 2 types:
a) Adherens junctions
b) Desmosomes

2) Cell – Matrix Anchoring Junctions:
• Link the cytoskeleton of a cell to ECM.
• 2 types:
a) Actin linked cell – matrix junctions (AKA focal adhesions)
b) Hemidesmosomes

Question 18

Anchoring Junctions Composition

Answer 18

I. Transmembrane adhesion proteins:
• 2 superfamilies:
— Cadherins (mediate cell – cell adhesion)
— Integrins (mediate cell – matrix adhesion)

II. Intracellular adaptor protein:
• Indirectly links adhesion proteins to cytoskeletal filaments

Question 19

There are two types of Cell – Cell Anchoring Junctions

Answer 19

Adherens Junctions & Desmosomes

Question 20

What are Adherens Junctions ?

Answer 20

they are multiprotein complexes that mediate cell-cell adhesion in all types of tissue.

• especially common in epithelial cells.

Question 21

Adherens Junction’s Structure

Answer 21

• AJs are built primarily from classical cadherins (Ca2+ -dependent, homophilic):
a ) Extracellular domains of cadherins on neighboring cells bind to each other.
b ) Intracellular domains of cadherins are linked to actin filaments via adaptor proteins (not shown).
c ) Cadherins bind to their partners with a relatively low affinity. Strong attachments result from the formation of many such weak bonds in parallel.

• AJs form a continuous belt that encircles entire epithelial cells.

Question 22

Adherens Junction’s Functions :

Answer 22

1 ) Promote adhesion of identical cells & further organization and separation of tissues during embryonic development (How?)
• Homophilic binding of cadherins leads to cell sorting, which is a crucial process in development.
— i.e., development of vertebrate nervous system

2 ) Enable tissues to withstand mechanical stress, thus maintain their integrity.
— i.e., physical trauma, cardiac muscle contraction, & flow within blood and lymphatic vessels.

Question 23

What are Desmosomes

Answer 23

they are structurally similar to adherens junctions, except they are composed of non-classical cadherins that are linked to intermediate filaments (IF) via adaptor proteins.

Question 24

Desmosomes Function

Answer 24

Maintain tissue integrity by providing mechanical strength.

Question 25

Where does Desmosomes express?

Answer 25

Present in most mature vertebrate epithelia and particularly abundant in tissues that are subject to high level of mechanical stress (i.e., heart muscle & epidermis).

Question 26

Types of IF:

Answer 26

• Keratin (most epithelial cells)
• Desmin (heart muscle cells)

Question 27

Desmosomes Vs Adherens Junctions

Answer 27

Desmosomes have a highly ordered structure in their extracellular region compared to adherens junctions.

Question 28

Actin Linked Cell – Matrix Junctions are also called :

Answer 28

Focal Adhesions

Question 29

Focal Adhesions Structure

Answer 29

• Transmembrane adhesion protein: integrin
— Heterodimers (α and β subunits)

• Extracellular ligand: ECM proteins
— Heterophilic binding

• Cytoskeletal attachment: actin filaments (via adaptor proteins)

Question 30

Focal Adhesions Functions

Answer 30

• Anchoring of actin cytoskeleton to ECM.

• Cell movement:
a ) Tissue regeneration & repair (wound healing)
b ) Embryonic development: (i.e., gastrulation, neural tube formation, neural crest cell migration)

Question 31

Integrins exist in two states:

Answer 31

• Inactive (folded, unbound)
• Active (extended, bound)

Question 32

Migrating cells must be able to

Answer 32

make and break attachments to the ECM
— this requires switching between activity states which is achieved by “inside-out” signaling.

• Steps:
1. Inactive conformation: ECM-binding pocket is masked.
2. Talin binds cytoplasmic domain of integrin β subunit
3. ECM-binding site gets unmasked, so integrin binds specific ECM proteins.
4. Integrin cytoplasmic domains and talin form a platform for the recruitment of other focal-adhesion proteins such as actin & vinculin (not shown) .
5. Focal adhesions involves clustering of active integrins (not shown).

Question 33

What are Hemidesmosomes

Answer 33

they are the most prominent cell-matrix junctions in epithelial cells acting as linkages between the ECM and intermediate filaments.

Question 34

Hemidesmosome’s structure

Answer 34

1) Transmembrane adhesion proteins:
— α6β4 integrin
— XVII collagen
2) Extracellular ligand: ECM proteins (laminin)
3) Cytoskeletal attachment: intermediate filaments (i.e., keratin)

Question 35

Hemidesmosomes Function

Answer 35

Facilitate stable adhesion of basal epithelial cells to the underlying basement membrane.

Question 36

Check the last two slides for summary ><

Answer 36

thank you for memorizing