Nuclear Organization and Structure

Question 1

Nuclear Envelope

Answer 1

2 phospholipid bilayers
- outer = continuous with ER
- inner = structural support by nuclear lamina

Question 2

Nuclear Lamin

Answer 2

Lamins – IF in nucleus (structural shape/support)
LAP, HP1, NPC
- connect to chromatin

Question 3

Types and Function of Lamins

Answer 3

A-type = alternate splicing of LMNA gene
- higher expression in skeletal/cardiac tissues

B-type = LMNB1 and LMNB2
- highly expressed in undifferentiated cells

LINCs – link lamins to cytoskeleton

Question 4

Laminopathies (mutations in Lamin A (LMNA) gene)

Answer 4

Muscular dystrophy = point mutation
Lipodystrophy = missense (adipose redistribution)
Charcot… = recessive (motor/sensory neuropathy)
Progeria = LMNA deletion (early onset aging)

Question 5

Lamins in Cancer

Answer 5

lamin A/C down-regulated in leukemias
- reduced A-type lamins = maleable nucleus (migration)

A-type lamins up-regualted in skin cancers
- support increase mechanical stress of solid tumours

Question 6

Nuclear Pore Composition

Answer 6

8 cytoplasmic filaments attached to cytoplasmic ring
nuclear ring
central transport channel
nuclear basket + terminal ring

Protein: Nucleoporins = cell-specific transport + signal changes

Question 7

Karyopherins

Answer 7

carrier proteins = active transport
- exportins (CRM1) – export NFAT from nucleus
- importins – import NFAT into nucleus

Question 8

Importins

Answer 8

• bind to TF in cytoplasm –> nuclear localization
• release TF when Ran-GTP binds (return to cytoplasm)
• Ran-GTP to Ran-GDP via GAPs = release of importin
• Ran-GDP back to nucleus, convert to Ran-GTP via GEFs

Question 9

Brownian Affinity Gate Model

Answer 9

macromolecules bind to nucleoporins increase residence time at entrance of tube