Moving into the nucleus Flashcards
What separates eukaryotes from prokaryotes?
The ability for the cell to compartmentalise distinct processes within organelles.
A cell is eukaryotic if it has membrane-bound nucleus and other organelles enclosed in a membrane.
How is modulating interactions by localistion to membrane bound compartments important?
Localisation enables the cell to modulate interactions between proteins.
This increases the relative concentrations of interacting species, more likely to see interaction or catalysis occurring.
How is regulation by localisation to membrane-bound compartments important?
Allows regulation of the local environment.
Transport of vesicles by motor proteins along the cytoskeleton, enabling regulation within distinct cellular domains.
e.g. Gene expression happens in nucleus of cell body, but proteins need to move into synapse for their function
How is a distinct environment by localisation to membrane-bound compartments important?
Provides a distinct environment allowing for specialised functions.
Lysosomes have a low pH for protein degradation.
How is protection by localisation to membrane-bound compartments important?
Protects the microenvironment from toxic metabolites.
e.g the mitochondria produces Reactive oxygen species, if not immediately converted to H2O2 by detoxifying enzymes it is dangerous.
By compartmentalising ROS cannot disrupt other cellular processes.
How is material exchanged between organelles?
Gated transport
Transmembrane transport
Vesicular transport
What is gated transport?
Occurs through pore complexes
Bidirectional between cytoplasm and nuclear pore complex
What is transmembrane transport?
Involves direct passage across intact membranes.
E.g. a diffusion gradient for small molecules.
Proteins usually require unfolding.
Happens between mitochondria, ER, Plastids, and Peroxisiomes between the cytosol
What is vesicular transport?
Does not involve passage across the membranes - involves fusion of membranes.
Exocytosis and endocytosis.
Secretory vesicles, linked to proteins having an N-terminal signal peptide - ER and Golgi transport
What is Swyer Syndrome?
SRY mutation, expressed on Y chromosome.
Mutation causes no expression of testosterone and expression of female gentalia, despite being genetically male (XY).
What does compartmentalisation of the nucleus do?
Separates genetic material from the rest of the cell.
Uncouples gene transcription from protein synthesis.
So the processes are highly regulated.
But the nucleus must communicate with the rest of the cell to enable gene expression.
What is the nuclear membrane?
A phospholipid bilayer.
Outer membrane is continous with ER.
Inner membrane has underlying meshwork of filaments - nuclear lamina.
What is the nuclear lamina?
A critical nuclear scaffold.
Creates and maintains structure intergrity.
Comprised of lamin (intermediate filaments), studded with lamin associated proteins (LAPs)
What is Lamin A?
Processing of mature Lamin A from pre-Lamin A is complex.
Farnesylation allows for rapid delivery of Lamin A to the nuclear envelope.
What is lamina for?
Gene regulation
NPC assembly
Chromatin function
Cell division
DNA replication
What do mutations in Lamin A do?
Causes premature aging syndrome Progeria.
Don’t get cleavage of C-terminal, causes changes in shape in nuclear architect and when cell divides - DNA damage.
What is the Nuclear Pore Complex?
NPC allows free movement of small molecules and selective transport of larger proteins - molecular sieve.
Nuclear pores are dismantled during mitosis and rebuilt after every cell cycle.
What is the NPC structure?
500 subunits of 30 nucleoporins (Nups).
Assembled in 8-fold symmetric structure that studs the double-nuclear membrane together.
Centre structure encases the transport channel.
Peripheral structures connect NPC to local environment.
What are the types of Nups?
Outer ring
Transmembrane
Inner ring - these 3 anchor NPC to nuclear membrane
FG Nups - unstructured, forms a hydrogel sieve.
Held in place by Linker Nups to centre of pore.
What are FG Nups?
Contain FG motifs - phenylalanine-glycine.
Interjected by spacer amino acids, allow for flexibililty.
Phenylalanine is aromatic, can form interactions with neighbouring phenylalanine.
Enables passage of proteins.
Why is the aromatic ring in FG nups important for hydrogel?
Mutation to a non-aromatic ring disrupts hydrogel barrier - nuclear pore becomes more porous.
Mutation to another amino acid with an aromatic ring preserves the hydrogel barrier, Van Der Vaals can still form.
How does movement occur within NPC?
Some by passive diffusion - metabolites, ions and small proteins.
Most by energy dependent transport - proteins, mRNA, tRNA, ribosomal subunits, viruses.
How is the import and export of proteins regulated?
The transport is a cycle between protein cargo, which interacts with nuclear transport receptors importins and exportins, and small GTPase Ran.
What is the process of import/export of proteins across the nuclear membrane?
Cargo is recognised and bound by NTRs.
The NTR-cargo docks on the NPC via FGnups. Cargo is translocated through the NPC.
The NTR-cargo is dissociated.
