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Thanh Cell Physiology Unit III > Nuclear Import & Export > Flashcards

Nuclear Import & Export Flashcards

1
Q

What is the name of the macromolecular pore that the nuclear membrane contains? How many?

A

~500-1000 Nuclear Pore complexes (NPC)

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2
Q

What does the Nuclear Pore complex contain?

A
  1. ~ 30 distinct nucleoporins (Nups)
  2. Membrane ring: (scaffold)
  3. Core scaffold
  4. cytoplasmic filaments
  5. Nuclear basket
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3
Q

3 distinct functions of NPC

A

Allow movement of moecules through nuclear membrane:

  1. diffusion through size filtering
  2. Spontaneous migration of amphiphilic molecules
  3. Facilitated transport
    • cargo associates with an amphiphilic molecule to get it in ;)
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4
Q

What are Karyopherins known as?

A 
Amphiphilic Cargo transporters 
aka
Cargo receptors
aka
Importins/Exportins
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5
Q

What repeats are found in Nups?

A

FG repeats

-serve as hydrophobic binding sites (filaments) for NPC

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6
Q

Basic principles of facilitated transport across pore complex (4)

A
  1. E dependent
  2. T dependent
  3. Signal dependant
  4. Saturable
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7
Q

What are the two families of karyopherins?

A
  1. Receptor family

2. Adapters

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8
Q

Overview of Receptor family Karyopherins

A
  1. Contain Ran-GTP binding domain.
  2. Binds with FG domains of nucleoporins (Nups)
  3. Another domain binding specific cargo/multiple cargos
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9
Q

Overview of Adapter Karypherins

A
  1. Capable of selecting different cargos

2. Increases efficiency of transport

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10
Q

NLS typically consists of which aa?

A

Basic motif: arginine + lysine rich

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11
Q

NES typically consists of which aa?

A

hydrophobic motif: Leucine rich

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12
Q

Why is Importin is typically considered as a heterodimer?

A

Importin usually an alpha beta pair.

Consists of an alpha (adaptor) and beta (transport receptor)

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13
Q

tRNA and miRNA use what type of export mechanism?

A

Ran dependent transport

tRNA:Exp-t

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14
Q

List different RNA that get exported and their respective export factors

A

tRNA:Exp-t
miRNA: Exp-5
snRNA: CRM1
mRNA: NXF1 + NXT1, Aly

rRNA: CRM1, NXF1+ NXT1

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15
Q

Describe mRNA export

A

Note: not part of Karyopherin family

  1. initiated by Aly linking premRNA to nuclear export
  2. allows recruitment of transport factors NXF1 + NXT1
  3. Remodeling by DB helicase removes ALY and forms export competent complex
  4. Kapα adaptor binds mRNA
  5. Kapβ transport receptor binds Kapα and mRNA
  6. Protein complex and nuclear export protein and nuclear basket interact and export occurs
  7. Once on the other side, a bunch of proteins associate with it and cause the complex to dissociate
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16
Q

mechanisms on how cargo nucleocytoplasmic transport is regulated in:

cargo

A
  1. Post translational modification
  2. Post transcriptional modification
  3. intermolecular/intramolecular masking
  4. affinity enhancement
  5. sequestration
17
Q

rRNA is ran dependent/independent transport

A

both
uses CRM1, NXF1+ NXT1

similar to snRNA and mRNA

18
Q

mechanisms on how cargo nucleocytoplasmic transport is regulated thru:

cargo

A
  1. Post translational modification
  2. Post transcriptional modification
  3. intermolecular/intramolecular interaction
19
Q

mechanisms on how cargo nucleocytoplasmic transport is regulated thru:

transport receptors

A
  1. expression
  2. sequestration
    • via entropy barriers created by Nups
    • Ran GTP/GDP can help overcome barrier
20
Q

mechanisms on how cargo nucleocytoplasmic transport is regulated thru:

NPC

A
  1. pore permeability

2. protein expression and stability

21
Q

Describe when it is necessary for BRCA2 to get imported into the nucleus and how it is able to stay localized in nucleus

A
  1. BRCA-RAD51 complex is transported into nucleus for DNA repair
  2. Complex is retained in nucleus bc NES on RAD51 is occluded by binding to BRCA2.
  3. BRCA2 NES is occluded by BSS1 binding during stressful conditions
22
Q

Give an example of how error in nuclear transport can contribute to breast cancer

A

A mutation from Asp to His in BRCA2 prevents binding with BSS1

- which means BRCA2's NES is exposed, and the mutant is rapidly exported    - RAD51 is also exported

Since BRCA2 is unable to stay in nucleus and function in DNA repair —> genomic instability –> breast cancer

23
Q

Give an example of how error in nuclear transport can prevent TSGs from doing its job?

A
  1. Normally TSG are localized in cytoplasm
  2. Under stressful conditions, TSG can go into nucleus and do its job
  3. Many tumors have upregulation of nuclear export proteins
    ie: CRM1 or MDM2 (exporting p53)
  4. Tumor suppressors are still functional, so selective inhibitors that can prevent export can restore tumor suppressor function

Thanh Cell Physiology Unit III (26 decks)

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