Import and Export from the Nucleus

Question 1

Name at least 8 types of molecules that are imported and exported from the nucleus

Answer 1

Imported: 
RNA polymerases
DNA polymerases
Protein kinases/ phosphates
Histones
RNA binding proteins
snRNAs
Transcription factors 

Exported: 
60s and 40s Ribosomal subunits
tRNA
mRNA
RNA binding proteins
snRNAs
Transcription factors

Question 2

What are the 3 layers of the Nuclear pore complex (NPC)?

Answer 2

Cytoplasm -> barrier layer -> scaffold layer -> membrane layer -> nucleus

Question 3

What distinct proteins help to form the subcomplexes of NPCs?

Answer 3

Nucleoporins (nups)

Question 4

What feature helps proteins enter neucleus?

Answer 4

Ability to interact with FG repeat -> bind and gradually move into cell

Question 5

What are the two important types of karyopherin import receptors?

Answer 5

karyopherin Beta (beta-importin - cargo specific)
heterodimeric import receptors (Alpha and beta importins - work together to bring in proteins)

Question 6

Where is RanGTP located? RanGDP?

Answer 6

RanGTP: nucleus
RanGDP: cytoplasm

Question 7

What happens when an importin bound to its cargo encounters RanGTP?

Answer 7

Releases cargo

Question 8

What is required fro exportins to bind their cargo?

Answer 8

RanGTP

Question 9

What are the targeting signals for molecules bound in or out of the nucleus?

Answer 9

In: Nuclear localization signal NLS
Out: Nuclear export signal NES

Question 10

What types of pathological conditions can nuclear trafficking defects cause?

Answer 10

developmental defects
cancer
infectious disease
autoimmunity
cardiac disease
neurodegenerative disease (AD & ALS)

Question 11

What pathology does human Nup 155 cause?

Answer 11

AF -> cardiac disorder characerized by clinical arrhythmia

Question 12

What pathology does human Nup 62 cause?

Answer 12

Autosomal recessive infantile bilateral striatal necrosis (degeneration of basal ganglia

Question 13

What pathology does human Nup 358/ RanBP2 cause?

Answer 13

familial cases of infection acute necrotizing encephalophathy

Question 14

What pathology does human Nup88 cause?

Answer 14

breast and ovaian cancers

Question 15

Name at least 3 mechanisms of regulating nuclear transport

Answer 15

stimulation dependent nucleocytoplasmic transport
- binding on surface of cell triggers/ inhibits import/export

Intramolecular masking
- fold protein so NES/NLS not visible

Intermollecular masking
- bind to substrate that conceals NLS/NES

Affinity enhancement
- add cofactors to increase binding affinity

sequestration

binding to cytoskeleton

binding to chromatin

Question 16

How does male to female sex reversal occur?

Answer 16

when mutates SRY region cannot enter nucleus -> cannot initiate transcription of male genes

Question 17

How are Nups related to cancer?

Answer 17

Often fused in cancerous cells

-lead to unregulated expression?