Nucleus

Question 1

Describe the general structure of the Nucleus

Answer 1

OM - Perinuclear Space - IM - Nucleoplasm
OM and Perinuc Space continuous with ER. OM cyto supported by IF and studded with ribosomes. Crossed by NPCs
IM supported by Nuc Lamina
Nucleoplasm = matrix and substructures (maj=nucleolus). Matrix includes RNPs

Question 2

Describe Nucleus Function and Compart

Answer 2

Contains nuclear genome, protects DNA, genome processing. Regulates translocation of TFs and seps mRNA from ribosomes. Concentrates enzymes and substrates to functional compartments. Relative size varies (myocytes many RBC none). Heterochromatin (dark and periph) Euchromatin (transparent and central)

Question 3

Describe NPCs

Answer 3

Nucleoporins are glycoproteins (3x8 proteins + plug). Bidrectional communication. Passive transport for small molecules. Active and selective for macromolecules, need G-protein

Question 4

Describe G-proteins

Answer 4

5 families: RAS, RHO, RAB, RAN, ARF

Off = GDP (GAP T-D in cyto). On = GTP (GEF in nuc)

Question 5

What is imported into nucleus

Answer 5

Proteins (histones, poly, TF), snRNP, snoRNP

Question 6

Describe the process of importing a structure

Answer 6

Cargo with NLS interacts with aplha and beta Importin which binds cargo to NPC and translocates. RAN-GTP conformation changes beta importin releasing cargo to nuc. RAN-GTP and importin go back to cyto where RAN GAP hydrolyzes RAN-GTP dissociating from importin reverting conformational change.

Question 7

What is exported form nucleus

Answer 7

mRNA (form of hnRNA with protein complex), tRNA, and ribosomes

Question 8

What is the process of exporting a structure

Answer 8

RAN-GTP binds to exportin inducing a conformation change to accept cargo and bind to NPC translocating to cytoplasm. RAN-GAP hydrolyzes GTP dissociating complex and reverting conformation change. Exportin returns to Nuc.

Question 9

Describe the basics of Nuclear Lamina

Answer 9

Network of proteins made of Lamin = IF and lines IM. Formed by Lam B (LMNA gene) and Lam A/C (splice variants of LMNA which form heterodimers). Lamins bind to proteins associated with heterochromatin, Emerin and other IM proteins.

Question 10

Describe interaction of Lamin and Chromosomes

Answer 10

Anchor site for chromosomes, chromatin bound directly to IM and Lam at centromeres and Telomers therefore occupy a distinct region. Chrom - A/C - B - Emerin

Question 11

Describe Mitosis and Lamin

Answer 11

Lam phosphorylated by Cdk1 in prophase reducing Nucleus to vesicles with Lam B and free dimers of A/C. Inactivation of Cdk1 results in dephosphorylation and reassembly.

Question 12

Describe the Nucleolus

Answer 12

rRNA and ribo factory. Assembled around clusters of gene repeats and NORs. Dissociates during mitosis. Nucleoli are active nucleolus

Question 13

What are the parts of the Nucleolus

Answer 13

1. Fibrillar center - Ribo genes, non-active, NOR, pre - rRNA
2. Pars Fibrilosa - transC of rRNA, mod by snoRNPs
3. Pars Granulosa - rRNA assembly into subunits for exportation

Question 14

What are Gajal bodies/ Gems

Answer 14

SMN proteins present. snoRNA and snRNA produced and modified and exported to cyto to become sno and sn RNPs

Question 15

What are speckles

Answer 15

snRNP activity center involved in splicing

Question 16

What is the Nuclear Organizing Region

Answer 16

Contain rRNA genes in tandem arrays. Clustered at 13, 14, 15, 21, 22. Covered by poly 1 synth fibrils. rRNA precursor and fibrils = 45s and spliced to 18s, 5.8s, 28s (5s outside in cytoplasm)

Question 17

Describe Laminopathies

Answer 17

Defects in Lamin/ Nuc Envelope. Skeletal and Muscular dystrophy results. Typically present during childhood. Results in fragile nuc envelope therefore stressed tissue is greatly affected. Disruption of nuc envelope results in abherrent distribution of chromosomes or altered interaction with TFs

Question 18

Describe Emery-Dreifuss Muscular Dystrophy

Answer 18

Mutation in Emerin or Lam A/C leading to flexion deformities, muscle weakness, conduction defects, arrythmias, and heart failure

Question 19

Describe Dilated Cardiomyopathy

Answer 19

Lam A/C defect leading to fragile nuc lam - cell death - congestive heart failure

Question 20

Describe lipidystrophy

Answer 20

Lam A/C defect leading to poor adipocyte differentiation leading to accumulation of fat in head and neck and peripheral muscle prominence

Question 21

Describe Hutchinson Gilford Progeria

Answer 21

Premature aging. Defect in Lam A leading to unstable NE (bleb formation, loss of periph heterochromatin, NPC clustering). Premature cell death LE = 13 yrs

Question 22

Describe Spinal Muscular Dystrophy

Answer 22

3 types (child, inter, adult). Gems with SMN defect therefore snRNP and pre-mRNA splicing defects leading to loss of MNs in spine and stem. Sudden onset