Nucleus Flashcards
Describe transport in the nucleus?
Bidirectional, selective transport of proteins through NPCs.
What are the three structures of the nucleus?
Inner nuclear membrane, outer membrane, perinuclear space (space between inner and outer membrane).
What are nuclear pore complexes made of?
Around 30 different proteins arranged in octagonal symmetry, with one or more aqueous passage.
What is responsible for the selectivity of the active import process into the nucleus?
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.
How is macro molecular transport different in NPCs to other membranes?
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.
What do nuclear localisation signals do?
Recognise nuclear localisation signals and bind to both the signal on the protein to be imported and to NPC proteins.
What are FG-repeats?
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.
What happens to import receptors upon entry into the nucleus?
They dissociate from the protein and return to the cytosol.
What are adaptor proteins?
Proteins required to bind the import receptors to the protein to be transported.
What is ran?
A monomeric GTPase found in both the cytosol and the nucleus.
What triggers GTP hydrolysis in what compartment?
GTPase-activating protein (GAP) in the cytosol.
What triggers GTP condensation in what compartment?
Guanine exchange factor (GEF) in the nucleus.
What does Ran-GTP do?
Binds to the nuclear side of the NPC and causes the release of cargo
What are laminopathies?
A group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina.
What are the main mutations in laminopathies?
Mutations in lamin A/C and nuclear lamina associated proteins.
Is there a cure for laminopathies?
No. Treatment is largely symptomatic and supportive.
What does emery-Dreifuss muscular dystrophy chiefly affect?
Skeletal and cardiac muscles. Joint deformities (contractures) which restrict joint movement, muscle weakness and wasting, heart problems.
What is the mutation that causes Hutchinson-Gilford progeria syndrome?
Point mutation in Lamin A gene.
What does the mutation in Hutchinson-Gilford progeria syndrome cause?
Abnormal protein incorporation into the nuclear lamina, leads to mechanical defect, thickening of the lamina, loss of peripheral heterochromatin and increased DNA damage.
What is progeria?
Physical aspects of ageing are accelerated therefore early onset.
What is triple A syndrome associated with and what is the mutation?
With the NPC and the mutation is ALADIN.
What does the mutation in triple A syndrome cause?
ALADIN integration into the NPC, which effects nuclear import of certain proteins which are involved in protecting and repairing DNA under oxidative stress.
What are the symptoms of triple A syndrome?
Autonomic dysfunction (heart rate and blood pressure), adrenal insufficiency, achalasia (muscle control in oesophagus and sphincter), mental retardation.
How are viruses associated with NPCs?
They can use the NPCs to deliver their genetic information for replication into the nucleus.
How do different viruses cross the NPC?
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.
What do numerous cancers contain abnormalities in?
Human transcription/export complex (hTREX)
What does hTTEX do?
Stabilises the mRNA and aid in efficient nuclear export.
What does a mutation in hTREX cause?
Enhances formation of R loops which halt transcription and increase DNA damage, DNA-RNA hybrid formation when newly transcribed RNA binds DNA template.
