Chapter 12 Nuclear Protein Transport

The nuclear envelope which is a bilayer membrane which contains pores that allow for bidirectional traffic.

The majority of the genomic material.

Site of DNA replication and RNA synthesis.

Continuous with the surrounding membrane of the ER. The space between the inner and outer nuclear membrane is continuous with the lumen of the ER.

Mammalian cell contains 3,000 to 4,000, each containing about 30 different proteins (nucleoporins). Nucleoporins assemble into a large complex of about 125 million daltons in mass. Have an 8 fold rotational symmetry.
Sit between the inner and outer nuclear membrane without disrupting their continuinity.
Responsible for bidirectional transport of molecules across nuclear membrane.

A subset of proteins called the nuclear lamins. They polymerize into a 2D network that sits just beneath the inner nuclear membrane.

They attach to proteins found in the nuclear pore and the inner membrane and interact with chromatin.
They provide a physical link between DNA and the nuclear envelope.

Column subunits form the side walls of the pore.
Annular subunits line the inner portion of the pore.
Lumenal subunits anchor the complex to the membrane.
Ring subunits flank both the cytosolic and nuclear faces of the complex.

8 cytosolic fibrils
8 nuclear fibrils that form a basket-like structure through attachment to a smaller ring like structure at its base.

1. Passive transport or diffusion

2. Facilitated, active, or gated transport.

1. Moecules less than 5kD in size can pass freely.
2. Nuclear envelope is not a barrier.
3. No difference in metabolite distribution between the cytosol and the nucleus.
4. Does not require receptosr and energy.
5. As size increases, transport through the pores slows down.

An energy requiring process.
GTP required for protein import and export
ATP required for mRNA export
Moves molecules against their concentratoin gradient.
Used by proteins larger than 60 kD.

1. Required energy from GTP
2. Temperature dependent
3. Signal sequence dependent
4. Saturable - a fixed amount of substrate is transferred in a given period of time.
5. All properties features of carrier or receptor mediated transport.

1. Formation of a cargo:carrier complex in the donor compartment.
2. Transport of this complex through the nuclear pore.
3. Release of the cargo in the target compartment and recycling of the carrier.

Donor and target compartment will vary depending on whether protein import or protein export is occuring.

1. Histones/DNA packaging proteins
2. DNA polyemrase
3. DNA repair enzymes
4. DNA modifying enzymes (methylase, topoiosomerase I and II, helicase, ligase)