E3L2: Junctions and ECM - Problem Set material

Question 1

Disease and pathogenesis?

Answer 1

Pemphigus. Autoantibodies directed at a cadherin called “desmoglein” in skin.

Question 2

Pemphigus MAINLY affects which cytoskeletal filament network?

A. Actin microfilaments

B. Cytokeratins

C. Microtubules

D. All of the above

Answer 2

Mainly B. Cytokeratins (an intermediate filament)

Note: actin filaments also retract, probably due to the linkage between these two networks.

Question 3

Take home message? Cancer?

Answer 3

Cadherin is required for cell-cell adhesion. Need both Cadherin and Ca++ for adhesion. Loss of cadherin promotes metastasis.

Question 4

Explain the meaning of “dominant negative” mutation, in the context of this picture:

Answer 4

Dominant negative mutations wreck the function of highly organized units, such as the collagen fibers shown.

Think: bad apple. One bad apple ruins the whole barrel.

Another example would be a mutation that ruins the actin thin filament network in muscle.

Question 5

Glycine to X mutation in Collagen. What effect?

Answer 5

Disrupt the sterics of the hydrophobic edge, so the fibers will have difficulty associating.

Question 6

Which type of filaments are expressed in a cell-specific manner?

A. Intermediate filaments

B. Actin filaments

C. Myotubules

D. Two of the above

See picture below.

Answer 6

A. Intermediate filaments

Question 7

Which of the following intermediate filament proteins are selectively expressed in MUSCLE?

A. Vimentin

B. Keratin

C. Lamins

D. Neurofilamental proteins

Answer 7

A. Vimentins

Question 8

ACTA1 is a muscle-specific actin. Mutations in one of these actins is an example of what kind of effect?

Answer 8

Dominant negative. Look how organized the actin is. Messing one up will ruin it for the rest!

Question 9

What’s the take home-message from this image?

Answer 9

Many proteins interact with actin. It’s highly conserved, and versatile. Don’t target actin with a drug!

Question 10

Tau proteins are important for organization of microtubules.

Hyperphosporylated tau is found in neurofibrillary tangles in affected neurons. Which of the following are correct, regarding the attached experiment?

A. Tau is more soluble in Alzheimer’s vs. control

B. Tau is more insoluble in Alzheimer’s vs. control

C. Soluble Tau is available to organize microtubules

D. Soluble Tau is unavailable to organize microtubules

Answer 10

B and D are correct.

Insoluble tau may precipitate in neurons and be unable to interact with microtubules.

Question 12

Regarding the Tau gel (again), inhibitiors of tau kinases may have which of the following effects?

A. May prevent tau hyperphosphorylation.

B. Prevent tau aggregation
C.Promote microtubules association
D. Slow or reverse progression of Alzheimer’s disease

E. All of the above

Answer 12

E. All of the above are true. Straight off the slide.