Protein of the Month

January 2007

MORE ON THIS MONTH’S PROTEIN	OTHER PROTEINS OF INTEREST
Molecule of the Month: Importins	ExPASy Protein Spotlight

Importins

By Jennifer McDowall

In eukaryotic cells, DNA is sequestered away from the rest of the cell in its own organelle, the nucleus. This arrangement facilitates cellular regulation, especially gene expression and cell signalling, through controlling the passage of molecules to and from the nucleus. Molecules pass through the double-layered nuclear membrane via tightly controlled ‘holes’ in the membrane, which are known as nuclear pore complexes (NPCs). The NPC forms an aqueous channel connecting the nucleus to the cytoplasm, and can be around 25nm wide, large enough to let large assemblies such as ribosomal subunits through. A typical vertebrate cell possesses between 1000 and 10,000 NPCs. Each NPC contains 30-50 different proteins, called nucleoporins, which form a physical passage through the membrane and mediate bidirectional transport of molecules to and from the nucleus.

Most small molecules, such as ions and small proteins, can pass through the NPC by passive diffusion alone. However, larger molecules, such as proteins, mRNA, tRNA and rRNA, must first associate with carrier molecules (karyopherins or nuclear transport receptors) that specialise in transporting a particular cargo through the NPC. Karyopherins can be divided into importins (import molecules into nucleus) and exportins (export molecules out of nucleus), however, some transport receptors act to both import and export molecules.

Importins, Controlling Movement into the Nucleus.

Once the nucleus exports mRNA to be translated in the cytoplasm, it then needs to import back those proteins that is requires to function, such as histones, ribosomal proteins needed for ribosome assembly, signalling proteins such as transcription factors, and splicing factors to process mRNA. Most large proteins are imported into the nucleus by importins, carrier molecules that recognize and transport cargo containing a nuclear localisation signal (NLS). Most importins are heterodimeric receptors, consisting of two subunits:

Ø Importin-alpha

· Adaptor protein for importin-beta

· Binds NLS on cargo

Ø Importin-beta

· Mediates interactions with NPC

· (Can sometimes bind cargo)

Importin-beta uses importin-alpha as an adaptor molecule to recognise the nuclear localisation signal in the cargo molecule, however in other pathways, importin-beta can also bind and transport the cargo by itself.

Next: Importing Molecules into the Nucleus