Lecture 23: Cell Junctions and Cell Adhesions

Question 1

How is stress transmitted in epithelial tissue vs connective tissue?

Answer 1

Question 2

4 Types of cell junctions in animal cells?

Answer 2

Question 3

Anchoring Junctions

Answer 3

– Include cell-cell and cell-matrix interactions

– Transmit external stress from across the plasma membrane to the underlying cytoskeleton

Question 4

Occluding Junctions

Answer 4

– Form a permeability barrier between cells in an epithelia sheet

Question 5

Channel forming Junctions

Answer 5

– Create cytoplasmic continuity between adjacent cells for the passage of small molecules

Question 6

Signal Relay Junctions

Answer 6

– Allows extracellular signals to be passed from one cell to another

– Some anchoring junctions and channel forming junctions also conduct signaling

Question 7

adherens junctions and desmosomes are ___

Answer 7

cell-cell anchoring junctions

Question 8

actin-linked cell matrix junctions and hemidesmosomes are____

Answer 8

cell-matrix anchoring junctions

Question 9

tight junctions are ___

Answer 9

occluding junctions

Question 10

Gap junctions are ___

Answer 10

channel forming junctions

Question 11

tight junction

Answer 11

seals gap between epithelial cells

Question 12

adherens junction

Answer 12

connects actin filament bundle in one cell with that in the next cell

Question 13

desmosome

Answer 13

connects intermediate filaments in one cell to those in the next cell

Question 14

gap junction

Answer 14

allows the passage of small water-soluble molecules from cell to cell

Question 15

actin-linked cell-matrix junction

Answer 15

anchors actin filaments in cell to extracellular matrix

Question 16

hemidesmosome

Answer 16

anchors intermediate filaments in a cell to extracellular matrix

Question 17

_____ link the cytoskeleton to extracellular structures

Answer 17

Transmembrane proteins

Question 18

Cell-cell interactions are mediated by the ____ family of transmembrane anchors

Answer 18

cadherin

Question 19

Cell-Matrix interactions are mediated by the ____ family of transmembrane anchors

Answer 19

integrin

Question 20

Anchoring Junctions function

Answer 20

• Provide mechanical strength

– Especially important to tissues encountering severe mechanical stress like heart, muscle, and skin

• Connect the cytoskeleton to neighboring cells or the extracellular matrix

Question 21

Anchoring Junctions are composed of what two main classes of proteins?

Answer 21

– Intercellular anchor proteins

– Transmembrane adhesion proteins

Question 22

Types of Anchor Junctions

Answer 22

– Adherens junctions

– Desmosomes

– Hemidesmosomes

– Focal Adhesions

Question 23

Cadherins

Answer 23

• Ca2+-dependent cell-cell adhesion
• Present in adherens junctions and desmosomes
• Found in virtually all cells and tissues

Question 24

Cadherin superfamily

Answer 24

Question 25

Cadherins mediate ____ adhesion

Answer 25

homophilic

Question 26

Cadherin structure and function

Answer 26

Question 27

How do cadherins play a role in development?

Answer 27

Cell with similiar subclasses of cadherins expressed on their surface stick together because of homophilic binding

Question 28

Cadherins mediate cell-cell adhesion by a homophilic mechanism

Answer 28

• Tissue culture cells (that normally do not express N or E-cadherins) can be made to express either N- or Ecadherin. ## Footnote • The resulting population self selects based on homophilic interaction of the individual cadherins

Question 29

Which proteins link cadherins to actin filaments?

Answer 29

* p-120 catenin * Beta-catenin * Alpha-catenin * vinculin

Question 31

Adherens junctions

Answer 31

* Connect bundles of actin filaments between cells * Can form adhesion belts (zonula adherens) in epithelial layers * Transmembrane adhesion proteins belong to the cadherin family * Intracellular anchoring proteins – Catenins – Vinculin – α-actinin • Cells must be attached by adherens junctions for tight junctions to form

Question 32

Adherens junctions structure

Answer 32

Question 33

Early formation of adherens junctions

Answer 33

Question 34

Mechanotransduction in an adherens junction

Answer 34

Question 35

Uses of adherens junctions in development

Answer 35

Question 36

Desmosomes

Answer 36

* Connect intermediate filaments between cells * The type of intermediate filament attached is cell type specific – Keratin filaments in most epithelial cells such as skin – Desmin filaments in heart muscle

Question 37

Transmembrane adhesion proteins of desmosomes belong to the cadherin family:

Answer 37

– Desmoglein ## Footnote – Desmocollin

Question 38

Intracellular anchoring proteins of desmosomes?

Answer 38

– Plakoglobin (γ-catenin) – Desmoplakin – Plakophilin

Question 39

Desmosome Model

Answer 39

Question 40

Hemidesmosomes

Answer 40

* “Half desmosomes” that connect intermediate filaments to the basal lamina * Morphologically similar to desmosomes Transmembrane adhesion proteins belong to the integrin family – Extracellular domain of the integrin binds to laminin (more later) • Intracellular anchor protein – Plectin

Question 41

Desmosomes and hemidesmosomes link to the ____ network

Answer 41

intermediate filament

Question 42

\_\_\_\_ mediate transient cell-cell adhesions in the bloodstream

Answer 42

Selectins

Question 43

Selectins

Answer 43

– Cell surface, carbohydrate binding proteins (lectins) – Ca2+-dependent cell-cell adhesion – L-selectins • While blood cells – P-selectins • Platelets – E-selectins • Activated endothelial cells

Question 44

The structure and function of selectins

Answer 44

Question 45

Cell Adhesion Molecules (CAMs)

Answer 45

• Cell surface transmembrane proteins – Cell-cell adhesion – Cell-matrix adhesion * Some are Ca2+-dependent, while others are Ca2+- independent * Initially identified using antibodies to cell surface molecules * Antibodies to key CAMs were capable of inhibiting cell-cell adhesion in the test tube

Question 46

Ig superfamily Cell Adhesion Molecules (CAMs) structure

Answer 46

Question 47

Tight Junctions

Answer 47

* Occluding junctions in vertebrates * Also known as Zonula occludens (ZO) * Provide a barrier role in most epithelia * Prevent protein and lipid diffusion in the plasma membrane allowing for polarization – Apical vs. basolateral membrane • Variable permeability barrier between cells – Cell type dependent, bladder epithelial tight junctions are 104 X less permeable to inorganic ions like Na+ than intestinal epithelia

Question 48

Tight junction model

Answer 48

Question 49

What are the tight junction proteins?

Answer 49

claudin and occludin

Question 50

Claudin and occludin also bind to peripheral membrane proteins called ___ proteins that anchor the sealing strands to the actin cytoskeleton

Answer 50

ZO

Question 51

ZO proteins form ____ at tight junctions

Answer 51

scaffolds

Question 52

Septate Junction

Answer 52

Occur in invertebrates like Drosophila Functionally similar to tight junctions Different in structure and appearance

Question 53

Gap junctions

Answer 53

* Most cells in most tissues are in communication with neighboring cells by gap junctions * Made up of membrane-spanning channel-forming proteins called connexins * The channels or connexons have a maximal pore size of ~ 1.5nm * Allow the passage of small molecules but not proteins – Inorganic ions, sugars, amino acids, nucleotides, etc

Question 54

Anatomy of Gap junctions

Answer 54

* Each connexin monomer has four membranespanning segments * Humans have 14 different connexin genes * Six monomers assemble into a connexon * Different connexin subunit assemblies can produce different connexons * Connexons from adjacent cells interact to form an intercellular channel

Question 55

Gap junction diagram

Answer 55

Question 56

Structure of Gap Junction

Answer 56

Question 57

Gap junctions have diverse functions

Answer 57

• Electrical synapse – Direct coupling allows the propagation of an action potential from one cell to another without the need for a chemical intermediate (much faster) • Sharing of metabolites helps coordinate activities – Glycogen breakdown in response to hormonal stimulation in the liver – Hepatocytes not directly stimulated by hormone (potentially several cell layers away from a capillary and the source of the hormone) detect a signal by sharing a second messenger through gap junctions • Communication during development

Question 58

Connexin turnover

Answer 58

Connexins are added to the edges and removed from the middle

Question 59

Regulators of gap junction permeability?

Answer 59

– pH – Cytosolic Ca2+ concentration – Extracellular signals • Some neurotransmitters like dopamine

Question 60

Why regulate gap junction permeability?

Answer 60

– Cells need a way to close down these connection to prevent widespread damage when one participant is damaged

Question 61

Plasmadesmota

Answer 61

“Plant Gap Junctions” Since plants have a rigid cell wall, a specialized structure is required to bridge it