Nuclear import receptors

• nuclear locational signals must be recognised by nuclear transport receptors
• most receptors are Karyopherins.

  karyopherins are proteins involved in transporting molecules between cytoplasm and nucleus
• receptors can use adapter proteins that form an import receptor/NLS bridge
• there is a variety of import receptors and adapters. the cells recognise the range of NLS
• import receptors are soluble cytosolic proteins which contain multiple low-affinity binding sites for FG repeats found in the unstructured domains of several nucleoporins
• FG repeats recruit import receptors and their found cargo proteins to the NPCs.

  import receptors then bind FG repeats the form the mesh inside the nuclear pore to disrupt interactions between the repeats
• receptor-cargo complex locally dissolves the gel-like mesh and can diffuse into and within the nuclear pore complex pore
• nuclear export of large molecules via NPCs depends on a selective transport system as it relies on nuclear export signals on the macromolecules to be exported.

  export receptors bind to both the export signals directly/via an adaptor and to the NPC proteins.

  import and export transport systems work in similar ways but in opposite directions:

  • import receptors bind their cargo molecules in cytosol to then release then in the nucleus and exported to cytosol for reuse
• in nuclear export, RAN is present in both cytosol and nucleus as it is required for the active transport of macromolecules into and out of nucleus via NPCs.

  RAN = RAs related nuclear protein - this is a GTP binding protein which is essential for translocation of RNA & proteins via NPCs