Nucleus and transport receptors Flashcards
Nuclear envelope
Separates nuclear and cytoplasmic compartments
Nuclear pore complexes mediate:
movement of nuclear proteins to the nucleus
mRNA to the cytoplasm
Nuclear import of proteins
Nuclear localisation signal (NLS) which is short and basic
Nuclear export of proteins
Nuclear export signal (NES)
What are transport receptors?
Karyopherins called importins/exportins
Give some examples of importins/exportins
Importin alpha/beta
CRMI (exporter)
TAP (exporter involved in mRNA export)
The entry and exit of large molecules from the cell nucleus is tightly controlled by …
Nuclear pore complexes
For large macromolecules, such as RNA, to enter the nucleus…
they must be associated with transport factors - nuclear transport receptors e.g. karyopherins (importins)
What does the Ran system control?
Direction of transport
What regulates the ability of importins and exportins to transport cargo?
GTPase
Ran
GTPase
enzyme that binds to GTP to hydrolyse it and form GDP. Ran has a different conformational state depending on whether it is bound to DTP or GDP.
Ran
RanGAP
RanGEF
Ran - Ras related nuclear GTPase
RanGAP- Ran has low intrinsic GTPase activity and must be stimulated by RanGAP to hydrolyse GTP in the cytoplasm.
RanGEF - Causes release of GDP from Ran allowing GTP to rebind in the nucleus
The Ran cycle
RanGTP - RanGRP (Catalysed by RanGAP)
RanGDP moves into nucleus
RanGDP to RanGTP (Catalysed by RanGEF).
RanGTP can move out the nucleus
Protein nuclear import
Nuclear receptor will bind a cargo protein
The receptor moves through the nuclear pore complex
RanGTP binds the receptor to release the cargo (induced conformational change)
Cargo protein has been delivered to the nucleus.
The Receptor-RanGTP complex is exported
GTP is hydrolysed so the RanGDP dissociates from the nuclear transport receptor.
