Nuclear import and export Flashcards
Structure of the nuclear pore complex
- octagonally symmetric cylindrical structure around the axis of transport and a planar pseudo-symmetry through the nuclear envelope
- internal diameter wider at ends than midplane
- 8 cytoplasmic filaments and a nuclear basket formed from 8 filaments that join into a distal ring
The nucleoporins are
a family of proteins which are the constituent building blocks of the NPC
A typical nucleoporin has a domain structure with an _______ terminus containing multiple copies of the motif _______ and a _______ terminus rich in _______
- N
- XFXFG (FG repeats)
- C
- heptad repeats characteristic for coiled-coil conformation.
Which model:
Barrier is a 3-D sieve formed from inter- and intra-molecular interactions of FG-Nups
Selective Phase/Hydrogel Model
Which model:
FG-Nups move vigorously back and forth to create a repulsive barrier with few stable cohesive contacts
Virtual Gate/Polymer Brush Model
Which Model:
- FG-Nups adopt a mixture of extended (“tree”) and collapsed (“shrub”) conformations.
- The ends of several “trees” can form cohesive contacts to create a central tunnel (zone 1) that acts as a hydrogel, with a second route closer to the walls (zone 2) acting as a virtual gate
Forest Model
Which Model:
FG-Nups coat the inner surface of the pore to form a hydrophobic surface o Hydrophilic unfolded chains extend into the central pore to create a selectivity filter
Reduction of Dimensionality Model
Recent work has shown that nucleoporins pull double duty as
transcription factors regulating the activity of genes active during early development
_______ may also be a potential marker for cancer. _______ and _______ are highly overexpressed in some cancers, including colon cancer and very aggressive forms of lung cancer.
- Nucleoporins
- Nucleoporins Nup214
- Nup88
Karyopherins are
the proteins that actually facilitate nuclear transport through the NPC. The act as mediators between the nuclear pore complex and the cargo being transported. They can act as importins or exportins
Karyopherins are heteromeric molecules composed two major types of components, _______ karyopherins and _______ karyopherins, that function together to transport molecules through the NPC
- alpha
- beta
Receptor family of karyopherins = _______. They directly interact with FG Nups, and some also interact directly with cargo
beta karyopherins
Adapter family of karyopherins = _______. They facilitate cargo-selective binding
alpha
Ran (RAs-related Nuclear protein) is a
small 25Kda protein that is involved in transport into and out of the cell nucleus. It is a member of the Ras superfamily
Ran is a _______ binding protein that is essential for _______
- GTP
- the translocation of RNA and proteins through the NPC
Ran exists in the cell in two nucleotide-bound forms:
GDP-bound and GTP-bound
_______ is converted into RanGTP through the action of regulator of chromosome condensation 1 (RCC1), the nucleotide exchange factor for Ran
-RanGDP
RanGDP is converted into RanGTP through the action of _______, the nucleotide exchange factor for Ran
regulator of chromosome condensation 1 (RCC1)
RanGDP is converted into RanGTP through the action of regulator of chromosome condensation 1 (RCC1), the _______
nucleotide exchange factor for Ran
Ran’s intrinsic GTPase-activity is activated through interaction with R_______, facilitated by complex formation with _______
- Ran GTPase activating protein (RanGAP)
- Ran-binding protein (RanBP)
_______ leads to the conversion of RanGTP to RanGDP, thus closing the Ran cycle
GTPase-activation
GTPase-activation leads to the conversion of _______ to _______, thus closing the Ran cycle
- RanGTP
- RanGDP
_______ can diffuse freely within the cell, but because RCC1 and RanGAP are located in different places in the cell, the concentration of RanGTP and RanGDP differs locally as well, creating _______ that act as signals for other cellular processes.
- Ran
- concentration gradients
RCC1 is located
inside the nucleus
RanGAP is bound to
the nuclear envelope I
This difference in location of the accessory proteins in the Ran cycle leads to a _______ RanGTP to RanGDP ratio inside the nucleus and an inversely _______ RanGTP to RanGDP ratio outside the nucleus
- high
- low
RanGTP =
nuclear export
In addition to a gradient of the nucleotide bound state of Ran, there is a gradient of the protein itself, with a _______ concentration of Ran in the nucleus than in the cytoplasm
higher
Cytoplasmic RanGDP is imported into the nucleus by the small protein _______, where _______ can then catalyze exchange of GTP for GDP on Ran
- NTF2 (Nuclear Transport Factor 2)
- RCC1
Ran is involved in the
transport of proteins across the nuclear envelope by interacting with karyopherins and changing their ability to bind or release cargo molecules
Cytoplasmic RanGDP is imported into the nucleus by the small protein NTF2 (Nuclear Transport Factor 2), where RCC1 can then catalyze exchange of _______ for _______ on Ran
- GDP
- GTP
Cargo proteins containing a NLS are bound by _______ and transported into the _______
- importins
- nucleus
Inside the nucleus, RanGTP binds to _______ and releases _______
- importin
- the import cargo
Cargo that needs to get out of the nucleus into the cytoplasm binds to _______ in a ternary complex with _______
- exportin
- RanGTP
Upon _______ outside the nucleus, the complex dissociates and export cargo is released
hydrolysis of RanGTP to RanGDP
Upon hydrolysis of RanGTP to RanGDP _______, the complex dissociates and export cargo is released
outside the nucleus
