Nuclear Import and Export Flashcards
Nuclear Pore Complex Structure
45 nm diameter. 300 different nuceloporins (Nups) forming subcomplexes with 500-1k Nups/pore
Membrane bound, scaffolding, and barrier Nups.
Lumenal ring between nuclear envelope membranes, outer and inner rings make core scaffold.
Barrier Nups extend into pore, phenylalanine and glycine residues create entropic barrier to hydrophilic molecules.
Karyopherins
Amphiphilic transport molecules that transport large hydrophilic molecules. Receptor family interacts with F/G hydrophobic residues, Adaptor family recognizes cargo via nuclear import/export signal and receptor karyopherins.
NTF2
transporter for Ran GDP
NXF1/NXT1
transporter for mRNA, rRNA
Ran in import
Importin brings in cargo, associates with RanGTP which causes conformational change to dissociate cargo. RanGTP and importin move to cytoplasm where RanBP causes RanGTP dissociation from importin. GTP hydrolyzed. RanGDP recognized by NTF2 which brings it to nucleus where GDP is replaced with GTP
Ran in export
Exportin requires RanGTP association to bind cargo. Complex moves to cytosol where RanBP causes dissociation of all 3 elements. GTP hydrolyzed and GDP is recognized by NTF2 and brought to nucleus where GDP is exchanged for GTP.
Mechanisms of nuclear import/export (3)
Diffusion of small molecules
Spontaneous migration of amphiphlic molecules
Facilitated transport of all other molecules via Karyopherins
mRNA export
this is coupledto mRNA processing, 5’ cap
Regulation of import/export (3)
Masking of nuclear import/export signals
Increasing affinity of NLS/NES via phosphorylation
Sequestration of cargo (ex binding in cytoplasm)
Nuclear transport and disease
BRCA1 and RAD51 mutations can cause them to be exported from nucleus
Disease in general happen with mislocalization through selectivity barrier or protein interaction complications
Asymmetry of NPCs
Cell-specific expression, established in cell cycle
