cell junctions Flashcards

1
Q

what are cell junctions

A

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

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2
Q

cell junctions are abundant in

A

epithelial tissue

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3
Q

What do cell junctions do ?

A

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

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4
Q

Classification of Cell Junctions:

A

By location:
• Cell – cell
• Cell – matrix

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

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5
Q

Occluding junctions =

A

Tight junctions

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6
Q

What are tight junctions ?

A

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

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7
Q

tight junction’s location

A

apicolateral borders of adjacent epithelial cells

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8
Q

Tight junction’s structure

A

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

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9
Q

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

A

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

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10
Q

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

A

the protein (tricellulin)

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11
Q

What is the functions of tight junctions

A

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.

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12
Q

Communicating junctions =

A

Gap junctions

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13
Q

What are gap junctions

A

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.

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14
Q

Where does gap junctions express ?

A

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

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15
Q

Gap Junction’s Structure

A

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

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16
Q

Gap Junction’s Functions

A

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

17
Q

what are the two anchoring junctions ?

A

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

18
Q

Anchoring Junctions Composition

A

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

19
Q

There are two types of Cell – Cell Anchoring Junctions

A

Adherens Junctions & Desmosomes

20
Q

What are Adherens Junctions ?

A

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

• especially common in epithelial cells.

21
Q

Adherens Junction’s Structure

A

• 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.

22
Q

Adherens Junction’s Functions :

A

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.

23
Q

What are Desmosomes

A

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.

24
Q

Desmosomes Function

A

Maintain tissue integrity by providing mechanical strength.

25
Where does Desmosomes express?
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).
26
Types of IF:
• Keratin (most epithelial cells) • Desmin (heart muscle cells)
27
Desmosomes Vs Adherens Junctions
Desmosomes have a highly ordered structure in their extracellular region compared to adherens junctions.
28
Actin Linked Cell – Matrix Junctions are also called :
Focal Adhesions
29
Focal Adhesions Structure
• Transmembrane adhesion protein: integrin — Heterodimers (α and β subunits) • Extracellular ligand: ECM proteins — Heterophilic binding • Cytoskeletal attachment: actin filaments (via adaptor proteins)
30
Focal Adhesions Functions
• 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)
31
Integrins exist in two states:
• Inactive (folded, unbound) • Active (extended, bound)
32
Migrating cells must be able to
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).
33
What are Hemidesmosomes
they are the most prominent cell-matrix junctions in epithelial cells acting as linkages between the ECM and intermediate filaments.
34
Hemidesmosome’s structure
1) Transmembrane adhesion proteins: — α6β4 integrin — XVII collagen 2) Extracellular ligand: ECM proteins (laminin) 3) Cytoskeletal attachment: intermediate filaments (i.e., keratin)
35
Hemidesmosomes Function
Facilitate stable adhesion of basal epithelial cells to the underlying basement membrane.
36
Check the last two slides for summary ><
thank you for memorizing