Term
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Definition
: largest membrane-bounded compartment in Eukaryotic cells
•10% of cell volume
•10 microm diameter
•Protects DNA from mechanical forces
•RNA processing occurs without
interference from ribosomes
•Organizes replication, transcription and
RNA processing
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Term
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Definition
1) Nuclear Envelope
-outer membrane
-inner membrane
2) Nuclear Pore Complex
3) Nuclear Lamina
4) Nucleolus
5) DNA associated proteins
-chromatin
-RNA & protein molecules
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Term
The nuclear envelope (NE)
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Definition
1. The nuclear envelope (NE)
•the inner and outer nuclear membranes together
with their luminal content
-continuous, but maintain distinct protein composition
-space between the outer and inner membrane is continuous with
ER space
fills with newly synthesized proteins
•the nuclear pore complexes that are embedded
in the double-membraned NE
•Nuclear lamina
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Term
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Definition
•Underlies the nuclear envelope
•Provides support and structure; allows for the structural integrity of the nucleus
•Meshwork of intermediate filament proteins (IF) called lamins
•Anchored to the nuclear pores and to the integral membrane proteins of the inner nuclear envelope
-The inner nuclear membrane is rich in lamin binding proteins
-The nuclear lamina also contains lamin binding proteins
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Term
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Definition
IF proteins (special class) Two types
•Type A: Lamin A, Lamin C and related forms (LMNA gene)
•Type B: B1 (LMNB1 gene), B2 and B3 (LMNB2 gene)
•B-type lamins are fundamental; A-type have more specialized functions
•carboxy terminal tail: CAAX
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Term
Phosphorylation of the lamin proteins |
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Definition
-prevents the head-to-tail assembly and provides a mechanism for the disassembly of the lamina during mitosis. After mitosis, the lamins are dephosphorylated and reassembled
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Term
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Definition
•maintain nuclear shape
• interact with chromatin to organize it
-distribution of lamin coincides with peripherally located chromatin
-lamins can bind to SARs (scaffold attachment regions)
•required for proper spatial arrangement of the NPCs
•lamins play a role in DNA replication, transcription and nuclear growth
•alterations in lamins correlate with changes in gene expression
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Term
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Definition
1.Ribosome factory (also other non-coding RNAs are produced/processed)
2.Large aggregate of macromolecules including the rRNA genes, precursor rRNAs, mature rRNAs,rRNA processing enzymes, ribosomal protein subunits and partly assembled ribosomes
3. Not membrane bound
4. rRNA genes play a role in forming the nucleolus
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Term
Nuclear Pore and the Nuclear Pore Complex |
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Definition
1.Nuclear pore traverses the inner and outer nuclear membranes
membranes fuse at the nuclear pores
typically 3000-4000 pores/nucleus
2. Nuclear pore complex (NPC)
- 125 million daltons
50-100 proteins (nucleoporins)
- gated-nuclear import and export
< 60 kDa pass by diffusion
Large proteins; active transport
3. Busy: actively dividing cell imports 106 histone molecules
from the cytosol every 3 mins., exports 6 newly assembled large and small ribosomal subunits per minute from the nucleus to the cytoplasm.
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Term
Transport through the NPC |
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Definition
1.Import; proteins involved in transcription, replication,
RNA processing
Required players:
receptors
ran (small GTPase)
Required signal: Nuclear localization signal (NLS)
2. Export; proteins that have to shuttle between the nucleus and the
cytoplasm (some transcription factors) and mRNA
Required players:
receptors
ran
Required signal: Nuclear export signal (NES)
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Term
Nuclear trafficking signals |
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Definition
•Nuclear localization signal (NLS)
basic amino acids
Example: PKKKRKV (single amino acid code).
-first evidence of nuclear import receptors; NLS from large T competitively inhibits nuclear import of NLS-bearing proteins
•Nuclear export signal (NES)
Leucine-rich
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Term
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Definition
-imposes directionality on transport through NPCs
-Ran shuttles in and out of the nucleus
-Ran exists in two different conformational forms
-Ran is regulated by two proteins
RanGAP- stimulates Ran to hydrolyze bound GTP
RanGEF- stimulates Ran to release GDP and bind GTP
(GEF; GTP exchange factor)
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Term
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Definition
- Completion of pre-mRNA splicing generates export-competent mRNA
-export receptor is a complex of proteins deposited when the mRNA has
been correctly spliced and poly A’d.
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Term
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Definition
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•Group of diseases associated with defects in Lamin A/C
1.Neuromuscular disorders
-Example: Emery–Dreifuss muscular dystrophy (EDMD)
2. Adipose tissue disease
3. Systemic diseases presenting with pronounced aging features
-Example: Hutchinson-Gilford Progeria Syndrome (HGPS)
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Term
Defect associated with HGPS
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Definition
•Mutations occur in the LMNA gene -causes an aberrant splicing event
•Forms a truncated pre-lamin A called progerin
•Progerin is not processed properly, accumulates in the nuclei
-changes in nuclear shape
-lobulation of the nuclear envelope
-thickening of the nuclear lamina
-clustering of nuclear pores
•Impairment of DNA damage repair
•Premature cellular senescence (aging)
•Impairment of mitosis
•Chromatin disorganization
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