Nucleus

Question 0

Describe transport in the nucleus?

Answer 0

Bidirectional, selective transport of proteins through NPCs.

Question 1

What are the three structures of the nucleus?

Answer 1

Inner nuclear membrane, outer membrane, perinuclear space (space between inner and outer membrane).

Question 2

What are nuclear pore complexes made of?

Answer 2

Around 30 different proteins arranged in octagonal symmetry, with one or more aqueous passage.

Question 3

What is responsible for the selectivity of the active import process into the nucleus?

Answer 3

Nuclear localisation signals: short sequences that are rich in positively charged amino acids, Lysine or Arginine, which often form loops or patches on the protein surface.

Question 4

How is macro molecular transport different in NPCs to other membranes?

Answer 4

It occurs through the aqueous pore rather than through membrane-spanning proteins. Allowing fully folded nuclear proteins to be transported, some do undergo reconstruction during transportation.

Question 5

What do nuclear localisation signals do?

Answer 5

Recognise nuclear localisation signals and bind to both the signal on the protein to be imported and to NPC proteins.

Question 6

What are FG-repeats?

Answer 6

Short amino acid sequences rich in phenylalanine and glycine binding sites of the import receptors that line the pathway through the NPC for the import of import receptors and bound proteins.

Question 7

What happens to import receptors upon entry into the nucleus?

Answer 7

They dissociate from the protein and return to the cytosol.

Question 8

What are adaptor proteins?

Answer 8

Proteins required to bind the import receptors to the protein to be transported.

Question 9

What is ran?

Answer 9

A monomeric GTPase found in both the cytosol and the nucleus.

Question 10

What triggers GTP hydrolysis in what compartment?

Answer 10

GTPase-activating protein (GAP) in the cytosol.

Question 11

What triggers GTP condensation in what compartment?

Answer 11

Guanine exchange factor (GEF) in the nucleus.

Question 12

What does Ran-GTP do?

Answer 12

Binds to the nuclear side of the NPC and causes the release of cargo

Question 13

What are laminopathies?

Answer 13

A group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina.

Question 14

What are the main mutations in laminopathies?

Answer 14

Mutations in lamin A/C and nuclear lamina associated proteins.

Question 15

Is there a cure for laminopathies?

Answer 15

No. Treatment is largely symptomatic and supportive.

Question 16

What does emery-Dreifuss muscular dystrophy chiefly affect?

Answer 16

Skeletal and cardiac muscles. Joint deformities (contractures) which restrict joint movement, muscle weakness and wasting, heart problems.

Question 17

What is the mutation that causes Hutchinson-Gilford progeria syndrome?

Answer 17

Point mutation in Lamin A gene.

Question 18

What does the mutation in Hutchinson-Gilford progeria syndrome cause?

Answer 18

Abnormal protein incorporation into the nuclear lamina, leads to mechanical defect, thickening of the lamina, loss of peripheral heterochromatin and increased DNA damage.

Question 19

What is progeria?

Answer 19

Physical aspects of ageing are accelerated therefore early onset.

Question 20

What is triple A syndrome associated with and what is the mutation?

Answer 20

With the NPC and the mutation is ALADIN.

Question 21

What does the mutation in triple A syndrome cause?

Answer 21

ALADIN integration into the NPC, which effects nuclear import of certain proteins which are involved in protecting and repairing DNA under oxidative stress.

Question 22

What are the symptoms of triple A syndrome?

Answer 22

Autonomic dysfunction (heart rate and blood pressure), adrenal insufficiency, achalasia (muscle control in oesophagus and sphincter), mental retardation.

Question 23

How are viruses associated with NPCs?

Answer 23

They can use the NPCs to deliver their genetic information for replication into the nucleus.

Question 24

How do different viruses cross the NPC?

Answer 24

Small viruses: do not need to dissemble their virus capsid and can bind importins to cross.
Large viruses: have to dissemble their capsid by binding to nucleoporin and histone complexes which initiate capsid disassembly.

Question 25

What do numerous cancers contain abnormalities in?

Answer 25

Human transcription/export complex (hTREX)

Question 26

What does hTTEX do?

Answer 26

Stabilises the mRNA and aid in efficient nuclear export.

Question 27

What does a mutation in hTREX cause?

Answer 27

Enhances formation of R loops which halt transcription and increase DNA damage, DNA-RNA hybrid formation when newly transcribed RNA binds DNA template.