Nuclear import and export Flashcards

1
Q

Structure of the nuclear pore complex

A
  • 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
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2
Q

The nucleoporins are

A

a family of proteins which are the constituent building blocks of the NPC

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3
Q

A typical nucleoporin has a domain structure with an _______ terminus containing multiple copies of the motif _______ and a _______ terminus rich in _______

A
  • N
  • XFXFG (FG repeats)
  • C
  • heptad repeats characteristic for coiled-coil conformation.
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4
Q

Which model:

Barrier is a 3-D sieve formed from inter- and intra-molecular interactions of FG-Nups

A

Selective Phase/Hydrogel Model

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5
Q

Which model:

FG-Nups move vigorously back and forth to create a repulsive barrier with few stable cohesive contacts

A

Virtual Gate/Polymer Brush Model

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6
Q

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
A

Forest Model

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7
Q

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

A

Reduction of Dimensionality Model

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8
Q

Recent work has shown that nucleoporins pull double duty as

A

transcription factors regulating the activity of genes active during early development

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9
Q

_______ 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.

A
  • Nucleoporins
  • Nucleoporins Nup214
  • Nup88
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10
Q

Karyopherins are

A

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

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11
Q

Karyopherins are heteromeric molecules composed two major types of components, _______ karyopherins and _______ karyopherins, that function together to transport molecules through the NPC

A
  • alpha

- beta

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12
Q

Receptor family of karyopherins = _______. They directly interact with FG Nups, and some also interact directly with cargo

A

beta karyopherins

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13
Q

Adapter family of karyopherins = _______. They facilitate cargo-selective binding

A

alpha

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14
Q

Ran (RAs-related Nuclear protein) is a

A

small 25Kda protein that is involved in transport into and out of the cell nucleus. It is a member of the Ras superfamily

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15
Q

Ran is a _______ binding protein that is essential for _______

A
  • GTP

- the translocation of RNA and proteins through the NPC

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16
Q

Ran exists in the cell in two nucleotide-bound forms:

A

GDP-bound and GTP-bound

17
Q

_______ is converted into RanGTP through the action of regulator of chromosome condensation 1 (RCC1), the nucleotide exchange factor for Ran

A

-RanGDP

18
Q

RanGDP is converted into RanGTP through the action of _______, the nucleotide exchange factor for Ran

A

regulator of chromosome condensation 1 (RCC1)

19
Q

RanGDP is converted into RanGTP through the action of regulator of chromosome condensation 1 (RCC1), the _______

A

nucleotide exchange factor for Ran

20
Q

Ran’s intrinsic GTPase-activity is activated through interaction with R_______, facilitated by complex formation with _______

A
  • Ran GTPase activating protein (RanGAP)

- Ran-binding protein (RanBP)

21
Q

_______ leads to the conversion of RanGTP to RanGDP, thus closing the Ran cycle

A

GTPase-activation

22
Q

GTPase-activation leads to the conversion of _______ to _______, thus closing the Ran cycle

A
  • RanGTP

- RanGDP

23
Q

_______ 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.

A
  • Ran

- concentration gradients

24
Q

RCC1 is located

A

inside the nucleus

25
Q

RanGAP is bound to

A

the nuclear envelope I

26
Q

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

A
  • high

- low

27
Q

RanGTP =

A

nuclear export

28
Q

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

A

higher

29
Q

Cytoplasmic RanGDP is imported into the nucleus by the small protein _______, where _______ can then catalyze exchange of GTP for GDP on Ran

A
  • NTF2 (Nuclear Transport Factor 2)

- RCC1

30
Q

Ran is involved in the

A

transport of proteins across the nuclear envelope by interacting with karyopherins and changing their ability to bind or release cargo molecules

31
Q

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

A
  • GDP

- GTP

32
Q

Cargo proteins containing a NLS are bound by _______ and transported into the _______

A
  • importins

- nucleus

33
Q

Inside the nucleus, RanGTP binds to _______ and releases _______

A
  • importin

- the import cargo

34
Q

Cargo that needs to get out of the nucleus into the cytoplasm binds to _______ in a ternary complex with _______

A
  • exportin

- RanGTP

35
Q

Upon _______ outside the nucleus, the complex dissociates and export cargo is released

A

hydrolysis of RanGTP to RanGDP

36
Q

Upon hydrolysis of RanGTP to RanGDP _______, the complex dissociates and export cargo is released

A

outside the nucleus