Nucleus Flashcards
Function of the nucleus
Compartmentalization of the cellular genome and its activities
○ Site of DNA replication, transcription, RNA processing
○ Site where translation components (ribosomes, mRNA, tRNA) are synthesized
Coordination of cellular activities
○ Control of metabolism
○ Protein synthesis
Reproduction (cell division)
Nuclear Subdomains
30+ specialized subdomains in nucleus
Not membrane bound
Nucleolus
Most obvious nuclear subdomain
Size and number (1-5 nucleoli) depend on the metabolic activity of the cells
Functions to produce ribosomes
□ Site of ribosomal DNA (rDNA) gene transcription, rRNA processing, and initial stages of ribosomal subunit (rRNA + protein) assembly
Final assembly of ribosomes (used for protein synthesis) occurs in the cytoplasm
Chromosomal Localization
Location of a gene is often related to its activity
Most actively transcribed genes are found at the periphery of a chromosomal subdomain
Interchromosomal Channels
○ Regions between domains that serve as barriers to prevent unwanted DNA-DNA or DNA-protein interactions
Active genes (chromatin) from different subdomains (or from different regions of the same chromosome) extend into interchromosomal channels to form transcription factories where TF are concentrated
Kissing Chromosomes
Interactions between interchromosomal channels
Gene regulatory regions from one chromosome can activate a gene on another gene
Nuclear Speckles
• Subdomains that appears as “speckles” via fluoresence microscopy
• mRNA splicing factors are concentrated here
○ Where pre-mRNA processing occurs
• Often located in interchromosoml channels next to transcription factors
• Numerous and highly dynamic
Can move quickly and grow/shrink depending on the needs of the cell
Nuclear Matrix
Insoluble fibrillar like protein network distributed throughout the nucleoplasm
Structural role
Serves as scaffold (Responsible for organizing nuclear subdomains and anchoring protein factors-i.e. DNA replication, RNA processing..etc)
Parts of Nuclear Envelope
Nuclear membranes
Nuclear lamina
Nuclear pore complex
Nuclear Membrane
Inner and outer membranes
- Phospholipid bilayers arranged in parallel (concentric)
Separated by nuclear envelope lumen
Outer Membrane
Continuous with RER
Ribosomes attached to the cytoplasmic surface of the outer membrane
Functionally similar to RER
Nuclear envelope Lumen
Continuous with ER lumen
Inner Membrane
Unique protein composition
Functionally distinct from outer membrane
NPC
Join outer and inner membranes
Regulates trafficking of all substances between nucleus and cytoplasm
- Small polar molecules (Nucleotides, ATP…etc)
- RNAs
- Proteins
Nuclear Lamind
Located on inner surface of inner membrane
Network “mesh” of long, filament like proteins
- ABC nuclear lamins
- Related to proteins that form part of the cytoskeleton in the cytoplasm (i.e. intermediate filaments)
Provides mechanical support to nuclear envelope
-Binds to nuclear inner membrane integral proteins
Serves as scaffold to chromatin and nuclear matrix attachment to the nuclear envelope
Hutchinson-Gilfod Progeria Syndrome
Mutation in lamin gene
Characterized by premature aging in children
§ Hair loss, wrinkles, artery damage
§ Death by adolescence
Due to a point mutation in the LAMIN A gene (LMNA) leading to a truncated lamin protein
Results in destabilization of nuclear lamina
§ Lamina serves as a contact site to bind the inside and outside of the nucleus
§ Causes changes in nuclear envelope morphology/ function
- Defects all over nucleus
Nups
Nucleoporins
Highly conserved among all eukaryotes (includes both integral and peripheral outer and inner membrane proteins)
Central Scaffold
Anchors complex to the nuclear envelope
Aqueous central channel
§ 20-40 nm wide pore
Inner surface of channel lined by “filament like” nups (FG nucleoporins)
Cytoplasmic Rings
Linked to central scaffold and cytoplasmic filament
Cytoplasmic filament
® Long protein filaments (nups) that extend into the cytoplasm
Involved in nuclear receptor-cargo protein recognition and import
Nuclear rings
Linked to central scaffold and nuclear basket
Nuclear basket
® Basket like structure made of nups located on the nuclear side of NPC
Also involved in nuclear receptor cargo protein important and export
FG Nucleoporins
Parge number of Phe-Glycine (FG) repeat sequences
FG domains possess a unique, highly disordered secondary structure
-Possesses an extended and flexible organization
Extend into the central channel
- Forming a hydrophobic “mesh” that limits the diffusion of macromolecules larger than 40 kDA (~39 nm in diameter)
Movement of Molecules Across NPC
Small molecules can move freely in both directions (Ntds)
Molecules >40 kDa unable to pass through NPC freely
-RNA and most proteins must be selectively imported/exported by an active process
Size Exclusion Limit For NPC
Based on studies using microinjected gold particles of varying sizes and coated with a nuclear protein
Coat small protein and see if it can pass through NPC, then increase in size until limit is determined
