What is the function of Ran-GTP?
A key function of the nuclear Ran. GTP is to support formation of complexes containing an export receptor (an exportin) and cargos such as RNAs, RNPs or proteins that are destined for export. In the cytoplasm, removal of the Ran. GTP from the complex results in its destabilization and release of the export cargo.
What is the Ran gradient?
The Ran Gradient also Controls Spindle Assembly Surprisingly, scientists discovered that the Ran gradient persists during the M-phase and is important for spindle assembly. Similar to its function in nucleocytoplasmic transport, Ran directs spindle assembly to the correct chromosome position in two ways.
What happens when Exportin binds ran-GTP?
Nuclear export Ran-GTP binds GAP and hydrolyzes GTP, and the resulting Ran-GDP complex is restored to the nucleus where it exchanges its bound ligand for GTP. Hence, whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.
Does GTP bind to Ran?
Ran is a small GTP-binding protein of the Ras superfamily regulating fundamental cellular processes: nucleo-cytoplasmic transport, nuclear envelope formation and mitotic spindle assembly.
How does nuclear GEF convert Ran-GTP to GDP?
Conversion between the two states is triggered by two Ran-specific regulatory proteins: a cytosolic GTPase-activating protein (GAP) that triggers GTP hydrolysis and thus converts Ran-GTP to Ran-GDP, and a nuclear guanine exchange factor (GEF) that promotes the exchange of GDP for GTP and thus converts Ran-GDP to Ran- …
Where is Ran-GTP located?
nucleus
Ran interacts with RanGAP in the cytoplasm, and with the chromatin-associated RCC1 in the nucleus. The specific location of these regulators creates a Ran-GTP gradient within the cell, with the net result of concentrating active Ran in the nucleus [1].
How does ran hydrolyze GTP?
Ran is a nuclear Ras-related protein that regulates both transport between the nucleus and cytoplasm during interphase, and formation of the mitotic spindle and/or nuclear envelope in dividing cells. Ran-GTP is hydrolysed by the combined action of Ran-binding proteins (RanBPs) and RanGAP.
Is ran an importin?
Ran and nucleocytoplasmic transport Karyopherins are either responsible for nuclear import (importins) or export (exportins). During nuclear import, an importin-α/β heterodimer forms a complex with cytoplasmic proteins tagged with a nuclear localisation sequence (NLS) and transports the proteins into the nucleus.
What role does Ran-GTP play in nuclear import?
It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase plays a role in the nuclear import in such a way that GTP-bound Ran dissociates importin:cargo complex in the nucleus and recycles importin back to cytoplasm.
How does Ran hydrolyze GTP?
Is RCC1 a GEF?
RCC1 is a chromosomal protein that functions as a GEF of the nuclear G protein Ran, which GTPase activity is enhanced by RNA1 located in the cytoplasm.
Why is Ran-GTP concentrated in the nucleus?
The high concentration of Ran-GTP in the nucleus promotes the disassembly of nuclear import complexes between proteins carrying a leucine-rich nuclear export signal (NES) and the transport factor Crm1, while dissociating nuclear import complexes formed between importins and cargo proteins carrying a lysine-rich nuclear …