Lecture 24

Question 1

What is the funciton of desmosomes?

Answer 1

Provides strong adhesion between epithelial and muscle cells

Question 2

What do desmosomes look like?

Answer 2

Disc-shaped (spots) between adjacent cells

Question 3

Who first identified desmosomes?

Answer 3

Inititally identified by Guilio Bizzozero
He was an Italian pathologist
Also identified and correctly assessed the function of platelets
Identified bone marrow as the site for BC

Question 4

What were desmosomes initially called?

Answer 4

Desmosomes were intitally called “Nodes of Bizzozero”

Question 5

Who named the term “desmosomes”?

Answer 5

Josef Schaffer coined the term “desmo” meaning bond and “soma” meaning fastening (body)

Question 6

What is the function of the molecular components of desmosomes?

Answer 6

Confer mechanical strength to tissues

Question 7

What are some desmosome diseases?

Answer 7

Desmosome diseases –> major blistering

Question 8

What are some transmembrane proteins in desmosomes?

Answer 8

Desmocollin and Desmoglein

Question 9

What do these transmembrane proteins do?

Answer 9

Used to link plasma membrane together
They are desmosomal cadherins
Calcium dependant
Cadherins have 5 extracellular domains

Question 10

How do desmocollin and desmoglein interact?

Answer 10

Desmocollin can interact with Desmoglein (eg. DSC1 interacts with DSG2)

Question 11

How many of these genes do mammals have?

Answer 11

3 desmocollin genes
4 desmoglein genes

Question 12

Which of the two are alternatively spliced?

Answer 12

Desmocollin genes are also alternatively spliced

Question 13

What are in most desmosomes?

Answer 13

Desmocollin 2 and desmoglein 2 are in most desmosomes

Question 14

What happens in a Desmocollin-3 null mouse?

Answer 14

The mouses skin ripped off when it was born at the site of the wound, the desmosomal plaque does not connect to the other side which leads to skin ripping off
Everything is fine until there is mechanical stress

Question 15

What is the desmocollin-3 site-directed skin null mouse?

Answer 15

Select the gene that is only found in the skin, and make the knock-out occur there, internally the mouse is fine but the skin rips off

Question 16

What did the baby mice cause in the Desmoglein-3 null mouse?

Answer 16

Baby mice caused nipple erosion on the mother mouse
D and E- no mechanical force
B- the rips in the cells

Question 17

What is Plakoglobin also known as?

Answer 17

Y (gamma) catenin

Question 18

What is the function of plakoglobin?

Answer 18

Links desmocollin and desmoglein to desmoplakin, plakophilin, and intermediate filaments
Binds to the intracellular cadherin specific domain (ICS) of the desmocollins and desmogleins

Question 19

What does PKP1 (Plakophilin) do?

Answer 19

PKP1: binds to desmoglein, desmoplakin and intermediate filaments
Thought to be responsible for clustering the proteins that make the electron dense plaque of the desmosomes

Question 20

What is the clinial disease of PKP?

Answer 20

People with mutations to PKP1:
Ectodermal dysplasia- affects development of teeth, nail, sweat glands and hair
Skin Fragility Syndrome- huge amount of skin blistering (fragile)

Question 21

What are mutations in PKP2 null mice like?

Answer 21

PKP2 null mice are embryologically lethal due to cardiac defects and “fragility of the myocardium”
Intermediate filaments release as it can’t bind well through desmoplakin

Question 22

What is the most abundant protein at the desmosome?

Answer 22

Desmoplakin

Question 23

What is desmoplakin needed for?

Answer 23

Needed to anchor the desmosome plaque to intermediate filaments

Question 24

What are the 2 proteins in desmoplakin?

Answer 24

Desmoplakin 1 (250kD) and desmoplakin 2 (251kD)

Question 25

Why is desmoplakin so important?

Answer 25

Very important for maintaining the heart because it is at intercalated discs (joins cardiomyoctes together)

Question 26

Do KO desmoplakin mice die?

Answer 26

KOs die at E6.5, have less desmosomes

Question 27

Do desmosomes bind to intermediate filaments?

Answer 27

Desmosomes that exist do not bind to intermediate filaments

Question 28

What is the similarity and difference between desmosomes and hemidesmosomes?

Answer 28

Hemidesmosomes and desmosomes morphologically look similar, but are very different at the molecular levels

Question 29

What kind of adhesion do desmosomes and adherens junctions use?

Answer 29

Demsosomes (and adherens junctions) use cadherin based adhesion

Question 30

How do hemidesmosomes bind to the ECM?

Answer 30

Hemidesmosomes use integrins to attach the intermediate filaments cytoskeleton to the extracellular matrix (Laminin) at the base of the cell

Question 31

What are integrins?

Answer 31

Many types in the cells

Question 32

What is the integrin Alpha6beta4 needed for?

Answer 32

Alpha6beta4 needed for hemidesmosome assembly and stability

Question 33

What can alter Alpha6beta4 integrin signalling?

Answer 33

The absense of Keratin 8 and 18 intermediate filaments can alter Alpha6beta4 integrin signalling and enhance cell migration

Question 34

What does less keratin mean?

Answer 34

Less keratin= less hemidesmosome= faster cell motility

Question 35

What is Laminin?

Answer 35

Many types, but Laminin 5 is in the basal lamina (basement membrane)

Question 36

What is BPAG2?

Answer 36

It is a hemidesmosome
It is a collagen (specifically collagen 17A1)
It is named for bullous pemphigoid antigen-2, a skin dsease caused by autoantibodies to Collagen 17A